RESUMEN
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Recent literature has proposed two subgroups of PD. The "body-first subtype" is associated with a prodrome of isolated REM-sleep Behavior Disorder (iRBD) and a relatively symmetric brain degeneration. The "brain-first subtype" is suggested to have a more asymmetric degeneration and a prodromal stage without RBD. This study aims to investigate the proposed difference in symmetry of the degeneration pattern in the presumed body and brain-first PD subtypes. We analyzed 123I-FP-CIT (DAT SPECT) and 18F-FDG PET brain imaging in three groups of patients (iRBD, n = 20, de novo PD with prodromal RBD, n = 22, and de novo PD without RBD, n = 16) and evaluated dopaminergic and glucose metabolic symmetry. The RBD status of all patients was confirmed with video-polysomnography. The PD groups did not differ from each other with regard to the relative or absolute asymmetry of DAT uptake in the putamen (p = 1.0 and p = 0.4, respectively). The patient groups also did not differ from each other with regard to the symmetry of expression of the PD-related metabolic pattern (PDRP) in each hemisphere. The PD groups had no difference in symmetry considering mean FDG uptake in left and right regions of interest and generally had the same degree of symmetry as controls, while the iRBD patients had nine regions with abnormal left-right differences (p < 0.001). Our findings do not support the asymmetry aspect of the "body-first" versus "brain-first" hypothesis.
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Idiopathic Rem sleep Behavior Disorder (iRBD) is a significant biomarker for the development of alpha-synucleinopathies, such as Parkinson's disease (PD) or Dementia with Lewy bodies (DLB). Methods to identify patterns in iRBD patients can help in the prediction of the future conversion to these diseases during the long prodromal phase when symptoms are non-specific. These methods are essential for disease management and clinical trial recruitment. Brain PET scans with 18F-FDG PET radiotracers have recently shown promise, however, the scarcity of longitudinal data and PD/DLB conversion information makes the use of representation learning approaches such as deep convolutional networks not feasible if trained in a supervised manner. In this work, we propose a self-supervised learning strategy to learn features by comparing the brain hemispheres of iRBD non-convertor subjects, which allows for pre-training a convolutional network on a small data regimen. We introduce a loss function called hemisphere dissimilarity loss (HDL), which extends the Barlow Twins loss, that promotes the creation of invariant and non-redundant features for brain hemispheres of the same subject, and the opposite for hemispheres of different subjects. This loss enables the pre-training of a network without any information about the disease, which is then used to generate full brain feature vectors that are fine-tuned to two downstream tasks: follow-up conversion, and the type of conversion (PD or DLB) using baseline 18F-FDG PET. In our results, we find that the HDL outperforms the variational autoencoder with different forms of inputs.
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We have studied at the ultrastructural level the presence of manganese (Mn) in rat basal ganglia, which are target regions of the brain for Mn toxicity. The rats underwent a moderate level of Mn exposure induced per os for 13 weeks. Mn was detected by means of electron spectroscopy imaging (ESI) and electron energy-loss spectroscopy (EELS) analyses on perfusion fixed samples embedded in resin. While no significant contamination by exogenous Mn occurred during the processing procedures, less than 50% of endogenous Mn was lost during fixation and dehydration of the brain samples. The residual Mn ions in the samples appeared as discrete particles, localized in selected sub-cellular organelles in a cell, suggesting that no significant translocation had occurred in the surrounding area. In control rats, the Mn sub-cellular localization and relative content were the same in neurons and astrocytes of rat striatum and globus pallidus: the Mn level was highest in the heterochromatin and in the nucleolus, intermediate in the cytoplasm, and lowest in the mitochondria (p<0.001). After chronic Mn treatment, while no ultrastructural damage was detected in the neurons and glial cells, the largest rate of Mn increase was noted in the mitochondria of astrocytes (+700%), an intermediate rate in the mitochondria of neurons (+200%), and the lowest rate in the nuclei (+100%) of neurons and astrocytes; the Mn level in the cytoplasm appeared unchanged. EELS analysis detected the specific spectra of Mn L(2,3) (peak at DeltaE = 665 eV) in such organelles, confirming the findings of ESI. Although a consistent loss of Mn occurred during the processing of tissue samples, ESI and EELS can be useful methods for localization of endogenous Mn in embedded tissues. The high rate of Mn sequestration in the mitochondria of astrocytes in vivo may partly explain the outstanding capacity of astrocytes to accumulate Mn, and their early dysfunction in Mn neurotoxicity. The high level of Mn in the heterochromatin and nucleoli of neurons and astrocytes in basal conditions and its further increase after Mn overload should provide insight into new avenues of investigating the role of Mn in the normal brain and a baseline for future Mn toxicity studies.
Asunto(s)
Ganglios Basales/efectos de los fármacos , Manganeso/metabolismo , Manganeso/toxicidad , Oligoelementos/metabolismo , Oligoelementos/toxicidad , Análisis de Varianza , Animales , Ganglios Basales/metabolismo , Ganglios Basales/ultraestructura , Citoplasma/efectos de los fármacos , Citoplasma/ultraestructura , Masculino , Microscopía Electrónica de Transmisión/métodos , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Neuronas/efectos de los fármacos , Neuronas/ultraestructura , Ratas , Ratas Wistar , Espectroscopía de Pérdida de Energía de Electrones/métodos , Fracciones Subcelulares/efectos de los fármacos , Fracciones Subcelulares/metabolismoRESUMEN
Protein-bound gamma-glutamylpolyamines have highlighted a new pathway in polyamine metabolism. Human foreskin keratinocytes offer a suitable model for this study. Indeed, they develop polymerized envelopes, as they differentiate, rich in epsilon-(gamma-glutamyl)lysine and N(1),N(8)-bis(gamma-glutamyl)spermidine cross-links. We have found that the selective oxidation of N(1)-(gamma-glutamyl)spermidine and N-(gamma-glutamyl)spermine by FAD-dependent polyamine oxidase (PAO) may be one of the cellular mechanisms regulating the preferential formation of a sterically defined bis(gamma-glutamyl)spermidine cross-link. The significance of this finding is unknown, but it suggests that the target of this PAO-modulation is to achieve the biochemical prerequisite for production of a normal epidermal stratum corneum.
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Flavina-Adenina Dinucleótido/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/metabolismo , Espermidina/análogos & derivados , Transglutaminasas/metabolismo , Animales , Diferenciación Celular , Reactivos de Enlaces Cruzados , Dimerización , Glutamina , Espermidina/química , Espermidina/metabolismo , Poliamino OxidasaRESUMEN
BACKGROUND: Considerable suffering is experienced by carers of patients with dementia. Most existing studies do not consider the coexistence of subjective and objective aspects that cause, interacting to each other, this suffering. OBJECTIVES: In this study we: (1) define the high-risk group of caregivers on the bases of the scores obtained on the four scales evaluating burden, distress, depression and anxiety (BDDA) taken into account simultaneously and (2) evaluate risk factors related to the high level of BDDA. SUBJECTS AND METHODS: 419 elderly outpatients with dementia and their caregivers were enrolled. Patients were evaluated for their cognitive, neuropsychological and functional impairment and for comorbidity. Caregivers were evaluated with four scales for the assessment of burden, distress related to neuropsychological disturbances, depression and anxiety. Cluster analysis was used to identify the group with the High level of BDDA (HBDDA). RESULTS: By multiple logistic analysis, disability, specific behavioural disturbances of the patients as well as caregiver's age, type of relationship and living in the south of Italy were observed to be a major risk factor for HBDDA. CONCLUSION: The targeted use of scales specifically assessing BDDA of the caregiver and the identification of particular patient and caregiver characteristics are able to allow a precise and early definition of caregivers at high risk of burden and distress. This might be helpful in planning the correct social/clinical/rehabilitative approach.
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Enfermedad de Alzheimer , Cuidadores/psicología , Estrés Psicológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Análisis por Conglomerados , Femenino , Humanos , Italia , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
In order to assess peripheral levels and activities of a broad spectrum of non-enzymatic and enzymatic antioxidants in elderly subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD), plasma levels of water-soluble (Vitamin C and uric acid) and of lipophilic (Vitamin A, Vitamin E and carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as activities of plasma and red blood cell (RBC) superoxide dismutase (SOD) and of plasma glutathione peroxidase (GPx) were measured in 25 patients with MCI, 63 AD patients and 53 controls. Peripheral levels and activities of antioxidants were similarly lower in MCI and AD patients as compared to controls. As MCI may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia.
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Enfermedad de Alzheimer/fisiopatología , Antioxidantes/análisis , Trastornos del Conocimiento/fisiopatología , Estrés Oxidativo/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/genética , Apolipoproteínas E/genética , Ácido Ascórbico/sangre , Carotenoides/sangre , Trastornos del Conocimiento/sangre , Eritrocitos/enzimología , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Masculino , Análisis por Apareamiento , Plasma/química , Valores de Referencia , Superóxido Dismutasa/metabolismo , Ácido Úrico/sangre , Vitamina A/sangre , Vitamina E/sangreRESUMEN
Atrial natriuretic factor (ANF) is a polypeptide able to affect cardiovascular homeostasis exhibiting diuretic, natriuretic, and vasorelaxant activities. ANF shows antimitogenic effects in different cell types acting through R(2) receptor. Excessive proliferation of smooth muscle cells is a common phenomenon in diseases such as atherosclerosis, but the role of growth factors in the mechanism which modulate this process has yet to be clarified. The potential antimitogenic role of ANF on the cell growth induced by growth factors appears very intriguing. Aim of the present study was to investigate the possible involvement of ANF on rat aortic smooth muscle (RASM) cells proliferation induced by known mitogens and the mechanism involved. Our data show that ANF, at physiological concentration range, inhibits RASM cell proliferation induced by known mitogens such as PDGF and insulin, and the effect seems to be elicited through the modulation of phosphatidic acid (PA) production and MAP kinases involvement.
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Aorta/efectos de los fármacos , Factor Natriurético Atrial/farmacología , Mitógenos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Antagonistas Adrenérgicos beta/farmacología , Animales , Aorta/citología , Aorta/metabolismo , Atenolol/farmacología , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , ADN/biosíntesis , Citometría de Flujo , Insulina/farmacología , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Ácidos Fosfatidicos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Until hospitals convert to 'filmless' radiology departments, computerized display and archival of x-ray images will necessitate devices to transform conventional X-ray films into digital images. Current methods for digitizing x-ray films include laser based and Charged Couple Device (CCD) based scanners. There is now much interest in the use of CCD devices for demanding applications, with the lower cost of ownership contributing towards the diffusion of CCD scanners. We report a study comparing the performance of three CCD based systems (an x-ray film digitizer, and two low cost flatbed scanners), looking at characteristic curve, useful optical range with respect the noise, repeatability, Modulation Transfer Function (MTF), and geometric distortion. In addition, we evaluated the potential and limitations of these devices in the clinical assessment of x-ray films. The most important weakness of CCD devices derived from the stability and the noise of CCD detectors, mostly affecting the useful optical range in the darker regions of x-ray films. Spatial resolution and geometric distortion were confirmed be the real points of strength of CCD technology. Therefore, the most appropriate system for each user depends on what type of clinical decision will be made following inspection of the digitised images.
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Intensificación de Imagen Radiográfica/instrumentación , Sistemas de Información Radiológica/instrumentación , Simulación por Computador , Humanos , Procesamiento de Imagen Asistido por Computador , Rayos Láser , Ruido , Procesamiento de Señales Asistido por ComputadorRESUMEN
Lispro (LP) and regular human (HR) insulins were compared in Type 1 diabetic (T1DM) patients on either a Mediterranean diet or normal diet. Twelve T1DM patients were recruited and randomized into two groups of 6, groups A and B. They were treated in different sequences (in 3-month intervals for 1 year). Group A: LP insulin and normal diet, LP insulin and Mediterranean diet, regular insulin and Mediterranean diet, regular insulin and normal diet. Group B: regular insulin and normal diet, regular insulin and Mediterranean diet, LP insulin and Mediterranean diet, LP insulin and normal diet. Each patient was treated with rapid acting insulin, either LP insulin or HR insulin, before each main meal and a dose of slow acting insulin at bedtime. Every 15 days the glycemic control, the incidence and frequency of hypoglycemic episodes, and any adverse events were evaluated. Every 3 months, hematology and a chemistry panel, pre- and post-prandial glycemic and insulinemic profiles were evaluated in all patients. HbA1c levels significantly decreased in LP patients on normal diet, post-prandial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards, 15-min post-prandial insulin levels higher in LP- than in HR-treated patients, and hypoglycemic episodes were significantly less in LP- than in HR-treated patients. LP insulin, irrespective of the type of diet, results in more effective glycemic control, significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet.
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Diabetes Mellitus Tipo 1/tratamiento farmacológico , Dieta , Hipoglucemiantes/uso terapéutico , Insulina/análogos & derivados , Insulina/uso terapéutico , Adolescente , Adulto , Área Bajo la Curva , Glucemia/análisis , Estudios Cruzados , Diabetes Mellitus Tipo 1/dietoterapia , Femenino , Hemoglobinas Anormales/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina Lispro , MasculinoRESUMEN
Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P=0.005). To avoid the influence of brachial artery size on FMD, the regression analysis was restricted to subjects with similar diameter (n=12). In these subjects wall shear stress continued to be significantly associated with FMD (r=0.69, P=0.01). Our results demonstrate a strong association between resting wall shear stress and FMD in the brachial artery in healthy men in vivo. This association is independent of age and vessel diameter.
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Arteria Braquial/fisiología , Vasodilatación/fisiología , Adulto , Anciano , Viscosidad Sanguínea/fisiología , Arteria Braquial/fisiopatología , Antebrazo/irrigación sanguínea , Humanos , Isquemia/fisiopatología , Masculino , Persona de Mediana Edad , Valores de Referencia , Flujo Sanguíneo Regional/fisiología , Estrés MecánicoRESUMEN
The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.
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Hipertensión/fisiopatología , Resistencia a la Insulina , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Adulto , Alelos , Glucemia/análisis , Femenino , Frecuencia de los Genes , Genotipo , Homeostasis , Humanos , Hipertensión/genética , Insulina/sangre , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio (WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.
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Tejido Adiposo/patología , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Obesidad/fisiopatología , Estrés Oxidativo , Acetilcolina/farmacología , Adulto , Combinación de Medicamentos , Femenino , Humanos , Indometacina/farmacología , Inyecciones Intraarteriales , Masculino , Nitroprusiato/farmacología , Vasodilatación , Vasodilatadores/farmacologíaRESUMEN
We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.
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Anticolesterolemiantes/uso terapéutico , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Endotelio Vascular/fisiopatología , Ácidos Heptanoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/fisiopatología , Pirroles/uso terapéutico , Acetilcolina/farmacología , Adulto , Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Atorvastatina , Velocidad del Flujo Sanguíneo , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Antebrazo/irrigación sanguínea , Humanos , Hipercolesterolemia/tratamiento farmacológico , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Nitroprusiato/farmacología , Pletismografía , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , omega-N-Metilarginina/farmacologíaRESUMEN
Computerised image analysis, performed on histological sections of (C57BL6/N) mouse lungs that had been intravenously (i.v.) injected with B16-F10 melanoma cells was used to develop a novel method to quantify the efficacy of potential antineoplastic drugs. This procedure allowed the evaluation of the rate of inhibition of growth and the anti-invasive capability of new molecules, thus resulting in more accurate data than that obtained from common macroscopical counting of surface metastatic foci. Several morphological parameters can be measured by this method: the percentage of tissue area occupied by metastases, which accounts for tumour implantation into the organ; the growth index, related to the size of the metastases, and the invasion index, related to the frequency of foci. These morphometric data were found to be correlated to the levels of lung hydroxyproline and transglutaminase activity, well known markers of tumour invasion and cell differentiation, respectively. The main objective of this computerised procedure was to evaluate how the tumour cell is affected in the host by the drug under investigation. The use of the method is exemplified by an analysis of the antitumour activity of some methylxanthines.
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Antineoplásicos/uso terapéutico , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias Pulmonares/secundario , Melanoma/secundario , Animales , División Celular , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Células Tumorales CultivadasRESUMEN
A common variant in the promoter of the human stromelysin gene, causing reduced enzyme expression, has been associated with the progression of coronary atherosclerosis. On the other hand, increased stromelysin activity may promote plaque rupture. The present study was undertaken to investigate the relationship between the genetic variation in the human stromelysin gene promoter and common carotid geometry. Forty-two healthy male subjects without major coronary heart disease risk factors were investigated. The polymorphism in the stromelysin gene promoter was studied through polymerase chain reaction amplification with the use of mutagenic primers. Age, blood pressure, lipids, glucose, viscosity, and body mass index were similar in homozygotes for the 5A allele (5A/5A), heterozygotes (5A/6A), and homozygotes for the 6A allele (6A/6A). Serum matrix metalloproteinase-3 levels did not differ significantly among genotypes. Common carotid diameters and intima-media thickness, measured by noninvasive ultrasonography, were significantly larger in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, diameter at the R wave was 0.63+/-0.09, 0.55+/-0.06, and 0.53+/-0.04 cm [mean+/-SD], P<0.005 by ANOVA; intima-media thickness was 765+/-116, 670+/-116, and 630+/-92 microm [mean+/-SD], P<0.05 by ANOVA). Wall shear stress, calculated as blood velocityxblood viscosity/internal diameter, was significantly lower in 6A/6A subjects (for respective 6A/6A, 5A/6A, and 5A/5A subjects, mean wall shear stress was 10.4+/-2.9, 13.5+/-3.5, and 12.6+/-1.9 dyne/cm(2) [mean+/-SD], P<0.05 by ANOVA). The results demonstrate that the gene polymorphism in the promoter region of stromelysin is associated with structural and functional characteristics of the common carotid artery in healthy male subjects without major risk factors for atherosclerosis. Individuals with the 6A/6A genotype (associated with lower enzyme activity) show a triad of events, namely, increased wall thickness, enlarged arterial lumen, and local reduction of wall shear stress, which might predispose them to atherosclerotic plaque localization.
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Arteria Carótida Común/diagnóstico por imagen , Variación Genética , Metaloproteinasa 3 de la Matriz/genética , Regiones Promotoras Genéticas , Adulto , Alelos , Arteriosclerosis/genética , Velocidad del Flujo Sanguíneo , Glucemia/análisis , Presión Sanguínea , Hemorreología , Heterocigoto , Homocigoto , Humanos , Lípidos/sangre , Masculino , Metaloproteinasa 3 de la Matriz/sangre , Persona de Mediana Edad , Polimorfismo Genético , Factores de Riesgo , UltrasonografíaRESUMEN
This work analyses the diagnostic capability of radiographic images taken from patients with total hip arthroplasty and visualised on monitor. Images were obtained with digital acquisition of conventional X-ray films. The investigated pathology is the absence of direct contact between bone and prosthesis (radiolucency). Three senior orthopaedists defined the diagnostic "truth" on well-defined regions of interest on 22 conventional X-ray films of total hip arthroplasty, obtaining a total of 110 reference ratings. Films were digitised by use of an X-ray scanner. Four readers evaluated the X-ray images, applying conventional and monitor visualisation. To show any difference between ratings on film and ratings on monitor a sensitivity, specificity and accuracy study jointly with a receiver operating characteristics (ROC) study were performed for each reader and for all combined readings. The intra-observer reproducibility of the radiographic protocol was equal to 87% and the inter-observer one was in the range 85-92%. The sensitivity, specificity and accuracy study together with the ROC analysis did not show significant differences between the two evaluation modes. The evaluation of radiolucency from digitised X-ray films visualised on a monitor resulted statistically comparable with the conventional evaluation on X-ray films.
Asunto(s)
Diagnóstico por Computador , Articulación de la Cadera/diagnóstico por imagen , Prótesis de Cadera , Complicaciones Posoperatorias/diagnóstico por imagen , Humanos , Variaciones Dependientes del Observador , Curva ROC , Radiografía , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.
Asunto(s)
Hipertensión/patología , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Remodelación Ventricular , Factores de Edad , Análisis de Varianza , Estudios de Evaluación como Asunto , Femenino , Genotipo , Humanos , Hipertensión/genética , Modelos Lineales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores SexualesRESUMEN
We validated the application of low-cost ISDN videoconferencing equipment for telemedicine. A telemedicine benchmark was designed and four different office videoconferencing systems were evaluated, all using basic-rate ISDN connections (128 kbit/s). All the low-cost systems showed generally good or acceptable performance for clinical use. We also investigated the feasibility of videoconferencing for an orthopaedic second-opinion service. Eight point-to-point conferences were conducted to discuss real clinical cases by use of interactive sharing of medical images. The average duration of each session was 35 min. Encouraging results were obtained.
Asunto(s)
Ortopedia/métodos , Telemedicina/instrumentación , Costos y Análisis de Costo , Estudios de Factibilidad , Humanos , Internet , Ortopedia/economía , Telemedicina/economía , Telemetría/economía , Telemetría/métodosRESUMEN
In this paper, we describe the 'Telemedicine Benchmark' (TMB), which is a set of standard procedures, protocols and measurements to test reliability and levels of performance of data exchange in a telemedicine session. We have put special emphasis on medical imaging, i.e. digital image transfer, joint viewing and editing and 3D manipulation. With the TMB, we can compare the aptitude of different video conferencing software systems for telemedicine issues and the effect of different network technologies (ISDN, xDSL, ATM, Ethernet). The evaluation criteria used are length of delays and functionality. For the application of the TMB, a data set containing radiological images and medical reports was set up. Considering the Benchmark protocol, this data set has to be exchanged between the partners of the session. The Benchmark covers file transfer, whiteboard usage, application sharing and volume data analysis and compression. The TMB has proven to be a useful tool in several evaluation issues.
Asunto(s)
Telemedicina , Benchmarking , Humanos , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Programas Informáticos , Telemedicina/métodos , Telemedicina/normas , Factores de TiempoRESUMEN
Investigation on the applicability of low-cost videoconferencing (VC) for health care services is becoming a real need. Reduced resources drive the administrators to evaluate inexpensive solutions for telemedicine. Considering this scenario, this work is a preliminary step to validate, from a technical point of view, if low-cost VC systems could be suitable for orthopaedic teleconsulting services. For this purpose, four different videoconferencing systems were tested. Each VC system was composed of a computer and a VC device installed in. VC devices were chosen among the most popular and distributed products (made by Intel, PictureTel and Aethra). The Telemedicine Benchmark, a specific tool defined by the authors, was applied to measure the overall systems performances in terms of time delays during basic rate ISDN connections (128 Kbit/s). Results showed that it is possible to apply low-cost videoconferencing systems for orthopaedic teleconsulting services. Most of the systems provided acceptable performance for medical image visualization and real time joint working. Further developments are recommendable to enhance the VC software tools capabilities and to improve software-user interface. reserved.