Impaired activation of Notch-1 signaling hinders repair processes of bronchial epithelial cells exposed to cigarette smoke.

Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis. The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes. Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay. Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes. In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells.

Comparing Methadone Rotation to Consensus Opinion.

CONTEXT: Methadone is a complex but useful medication for pain management in palliative care. Recent expert opinions have been published on the safe and effective use of methadone. OBJECTIVES: To determine the success of methadone rotations and evaluate concordance with consensus recommendations by a palliative care consult service. METHODS: A retrospective study of methadone rotation practice by a palliative care consult service and outcomes for patients hospitalized between January 1, 2012 and December 31, 2018 at a single academic medical center. A successful rotation was defined as a 30% reduction in pain or as-needed medication use sustained for at least three consecutive days. Patient outcomes were compared with expert consensus recommendations. RESULTS: About 59 patients met the inclusion criteria. The study population was mostly Caucasian men and women of equal proportions who were started on methadone for inadequate pain control. Sixty-eight percent of patients were successfully rotated. Subjects who were rotated using a standardized protocol were six times more likely to have a successful rotation (odds ratio 6.28 [1.25-30.92]; P = 0.0238). CONCLUSION: The utilization of a standardized protocol was associated with better patient outcomes.

Cigarette smoke extract modulates E-Cadherin, Claudin-1 and miR-21 and promotes cancer invasiveness in human colorectal adenocarcinoma cells.

BACKGROUND: Cigarette smoke is considered a risk factor for lung and colorectal cancer. A convincing link between epithelial-to-mesenchymal transition (EMT) with colorectal cancer progression and therapeutic resistance has emerged. Deregulated expression of E-Cadherin and Claudin-1 and increased miR-21 expression and invasiveness represent hallmarks of EMT. The effects of cigarette smoke exposure on EMT in colorectal adenocarcinoma cells are largely unknown. AIM: The aim of the study is to evaluate the effect of cigarette smoke extract (CSE) on miR-21, Claudin-1 and E-Cadherin, molecules associated to EMT in colorectal cancer cells. METHODS: A human colorectal adenocarcinoma cell line (Caco-2) was treated with CSE at different concentration (5% and 10%) and for different time points (3 h and 24 h). Metabolic activity (by MTS assay), cell necrosis/cell apoptosis (evaluating Propidium Iodide/Annexin V expression by flow cytometry), miR-21, Claudin-1 and E-Cadherin gene expression were evaluated by Real time PCR. Cell permeability, actin polymerization and cancer cell migration was assessed by Trans-Epitelial Electrical Resistance (TEER), Phalloidin expression and matrigel system, respectively. RESULTS: CSE at all the tested concentrations and at all time points reduced cell necrosis. CSE at 10% increased miR-21 and reduced the metabolic activity, cell necrosis, Claudin-1 and E-cadherin mRNA at 3 h. Cell permeability, actin polymerization and cancer cell migration were all increased upon CSE exposure. CONCLUSION: These results showed that CSE increasing miR-21, Claudin-1 and E-Cadherin and enhancing the aggressiveness of cancer cells, may concur to colorectal cancer progression.

Notch-1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps.

BACKGROUND: Alterations in the nasal epithelial barrier homeostasis and increased interleukin 33 (IL-33) expression contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). AIMS: As Notch-1 signaling is crucial in repair processes of mucosa, the current study assessed Notch-1/Jagged-1 signaling and IL-33 in the epithelium of nasal polyps biopsies from allergic (A-CRSwNP; n = 9) and not allergic (NA-CRSwNP; n = 9) subjects by immunohistochemistry. We also assessed, in a model of nasal epithelial cells, the effects of stimulation of Notch-1 with Jagged-1 on the expression of IL-33 (by flow cytometry, immunofluorescence, and immunocytochemistry), Jagged-1 (by flow cytometry), and p-CREB transcription factor (by western blot analysis). RESULTS: Ex vivo (a) in normal epithelium, the expression of Notch-1 and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (b) in metaplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (c) in hyperplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in A-CRSwNP than in NA-CRSwNP; and (d) in basal epithelial cells, no differences were observed in the expression of Jagged-1, IL-33, and Notch-1. The expression of Notch-1 significantly correlated with the expression of IL-33. In vitro, stimulation of Notch-1 with Jagged-1 induced the expression of (a) Jagged-1; (b) IL-33; and (c) p-CREB transcription factor. The inhibitor of Notch-1, DAPT, reduced all the effects of Jagged-1 on nasal epithelial cells. CONCLUSIONS: The data herein provided support, for the first time, a putative role of Notch-1/Jagged-1 signaling in the overexpression of IL-33 in the epithelium of nasal polyps from patients with CRSwNP.

EMG-based Indicators of Muscular Co-Activation during Gait in Children with Duchenne Muscular Dystrophy.

Muscular weakness is one of the main signs associated with the onset and progression of Duchenne Muscular Dystrophy. During motor functions, this disease also determines deviations in muscular activity, especially in terms of coordination and activation between muscles acting on the same joints. In this study, surface EMG activity of the lower limb muscles of 10 children with Duchenne Muscular Dystrophy at different times from disease onset were recorded along with kinematics during unconstrained gait. Muscular co-activation of muscle pairs was then evaluated by extracting different co-activation indicators, and linking them with kinematic markers of motor function. The combination of disease progression and pharmacological treatment resulted in a significant decrease in terms of co-activation indexes for two pairs of agonist-antagonist muscles, and for one of these two pairs the decrease in co-activation was correlated with a decrease in the motor function of gait.

Assessing the influence of SNR and pre-processing filter bandwidth on the extraction of different muscle co-activation indexes from surface EMG data.

Muscle co-activation is the mechanism that regulates simultaneous activity of agonist and antagonist muscles crossing the same joint. During functional movements, robust measurement techniques are required for an accurate determination of muscle co-activation, since various environmental and processing factors in the surface electromyography (sEMG) measurement process might influence the estimation of linear envelope profiles, and therefore the outcome of co-activation evaluated from the signal envelope. The aim of this study is to verify the performance of the co-activation indexes introduced in six different techniques used to assess muscle co-activation. A sensitivity analysis with respect to both noise and pre-processing choices for envelope estimation has been done by using a data-set of simulated sEMG signals. The results show how the indexes are affected by both the level of noise and pre-processing choices. The Vector Coding Technique and the Time-varying Multi-muscle approach perform better than the others in terms of both sensitivity to varying levels of co-activation and robustness to noise.

Measuring and benchmarking the quality of two different organizational ways in delivering infant vaccination.

The aim of this study was the quality of service evaluation of two different organizational ways in delivering infant vaccination according to a Regional Vaccination Plan. Eleven vaccination centres were selected in two Local Health Units (ASLs) belonging to the Regional Health Service of the Lazio Region, Italy. The services offering paediatric vaccinations for children under three years of age, delivered without an appointment (VACP) or with the need for an appointment (VACL), were investigated. The quality aspects under evaluation were communicational efficiency, organisational efficiency and comfort. Subjective data were collected from different stakeholders and involve the elicitation of best and worst feasible performance conditions for the ASLs when delivering VACP/VACL services. Objective data consists in the observation of current performances of the selected vaccination centres. Quality scorecards were obtained from the combination of all data. Benchmarking between VACP and VACL, i.e., two different organisational ways in delivering infant vaccination, can be performed as a result of the probabilistic meaning of the evaluated scores. An expert of vaccination services, i.e., a virtual combination of patients, doctors and nurses, claims the quality of service delivery of the ASLs under investigation with probability 78.03% and 69.67% for VACP and VACL, respectively. In other words, for short, the quality scores of the ASLs were 78.03% for VACP and 69.67% for VACL. Furthermore our results show how to practically improve the current service delivery. The QuaVaTAR approach can result in improvements of the quality of the ASLs for the two different ways of delivering paediatric vaccinations in a simple and intuitive way.

A Comparative Study on the Influence of Probe Placement on Quality Assurance Measurements in B-mode Ultrasound by Means of Ultrasound Phantoms.

To check or to prevent failures in ultrasound medical systems, some tests should be scheduled for both clinical suitability and technical functionality evaluation: among them, image quality assurance tests performed by technicians through ultrasound phantoms are widespread today and their results depend on issues related to scanner settings as well as phantom features and operator experience. In the present study variations on some features of the B-mode image were measured when the ultrasound probe is handled by the technician in a routine image quality test: ultrasound phantom images from two array transducers are processed to evaluate measurement dispersion in distance accuracy, high contrast spatial resolution and penetration depth when probe is handled by the operator. All measurements are done by means of an in-house image analysis software that minimizes errors due to operator's visual acuity and subjective judgment while influences of ultrasound transducer position on quality assurance test results are estimated as expanded uncertainties on parameters above (measurement reproducibility at 95 percent confidence level): depending on the probe model, they ranged from ±0.1 to ±1.9 mm in high contrast spatial resolution, from ±0.1 to ±5.5 percent in distance measurements error and from ±1 to ±10 mm in maximum depth of signal visualization. Although numerical results are limited to the two examined probes, they confirm some predictions based on general working principles of diagnostic ultrasound systems: (a) measurements strongly depend on settings as well on phantoms features, probes and parameters investigated; (b) relative uncertainty due to probe manipulation on spatial resolution can be very high, i.e. from 10 to more than 30 percent;

Cigarette smoke alters cell cycle and induces inflammation in lung fibroblasts.

BACKGROUND: Lung fibroblasts are crucial for the integrity of alveolar structure. Cigarette smoking, the major risk factor for chronic obstructive pulmonary disease, impairs the repair functions of lung fibroblasts. AIMS: The study simultaneously assessed for the first time cell cycle, p53, p21, p38, ERK 1/2 and IL-8. MAIN METHODS: Primary foetal lung fibroblasts (HFL-1) and primary lung fibroblasts from former (n = 5) and current (n = 5) smokers with/without cigarette smoke extracts (CSEs) and inhibitors of p38 and ERK1/2 were studied for cell cycle events and for marker expression by flow-cytometry, western-blot analysis and ELISA. KEY FINDINGS: CSE exposure did not induce caspase 3 cleavage or DNA laddering but reduced S phase, and increased G1 and G2/M in HFL-1. Furthermore CSE increased: p53 and p21 expression; p38 and ERK 1/2 pathway activation; and IL-8 release. Inhibitors of p38 and ERK 1/2 reversed the effects of CSE on cell cycle and on IL-8 release. ERK 1/2 inhibitor was able to reverse the effects of CSE on p21 expression. Primary lung fibroblasts from current smokers had higher ERK 1/2 activation in comparison to normal primary fibroblasts and higher percentage of cells in G1 phase and lower percentage of cells in S phase in comparison to former smoker fibroblasts. SIGNIFICANCE: Cigarette smoke may affect the reparative potential of lung fibroblasts altering the expression of p53 and p21 and the progression of the cell cycle to S phase. All these events are promoted by the activation of pro-inflammatory pathways.

Early surgery after coronary revascularization: a fine line between bleeding and thrombosis.

Management of PCI patients undergoing early surgery is still a matter of debate. Noteworthy, PCI patients require a dual antiplatelet therapy (DAPT), with aspirine and a thienopiridine (clopidogrel, prasugrel, ticagrelor), because of the high risk of stent thrombosis (ST), myocardial infarction (MI) and death, especially within the first month. Indeed, the number of surgical interventions after PCI is actually increasing, and physicians are looking for the best antiplatelet therapy management, in order to reduce both, bleeding and thrombosis risk. In this paper, current guidelines therapy management and new optional strategies to reduce the cardiovascular risk, related to early surgery, are discussed.

Coronary flow reserve evaluation: basics, techniques and clinical applications.

Coronary flow reserve is a useful physiologic parameter providing information on coronary stenoses severity. To date, the gold standard to evaluate coronary flow reserve consists of fractional flow reserve (FFR) measurement, assessed with a pressure-wire. The FFR has a high lesion specificity, due to insensitivity to patient hemodynamic status and to coronary microvascular resistance; it shows low inter- and intraindividual variability and a well-defined, bound cut-off range values (0.75-0.80). Several reports confirmed that FFR has high reproducibility and feasibility in patients with either single- or multi-vessel coronary artery disease, or with both stable and instable coronary artery disease and that is significantly associated with patient outcome. More recently, the FFR has been used as a sensitive marker of successful percutaneous coronary intervention, since postprocedural FFR value strongly predicts patients event-free survival rate after angioplasty. Moreover, it has been demonstrated that abnormal FFR ratios can be also associated with diffused atherosclerotic coronary artery disease in the absence of unique angiographically detectable stenoses requiring revascularization. There are strong evidences supporting that the FFR provides crucial functional information that could be related with morphological endovascular ultrasound findings, with the possibility to achieve same information in a cheaper, easier and more available manner. This review will focus on the current available literature regarding coronary flow reserve quantification and its clinical validation, suggesting and highlighting its current and future clinical applications.

Vascular smooth muscle cell dysfunction in patients with migraine.

BACKGROUND: Migraine is associated with increased risk of cardiovascular disease, but the mechanisms are unclear. OBJECTIVE: To investigate the activity of endothelial and vascular smooth muscle cells (VSMCs) in patients with migraine. METHODS: Case-control study of 12 patients with migraine without aura and 12 matched healthy control subjects. Endothelial and VSMC components of vascular reactivity were explored by plethysmography measurement of forearm blood flow (FBF) during infusions of vasoactive agents into the brachial artery. Forearm production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was also quantified. RESULTS: In patients with migraine, the vasodilating effect of acetylcholine (ACh), an endothelium-dependent vasodilator, was markedly reduced (p < 0.001 by analysis of variance). In response to the highest dose of ACh, FBF rose to 8.6 +/- 2.2 in patients with migraine and to 22.7 +/- 3.0 mL x dL(-1) x min(-1) in controls (p = 0.001). The dose-response curve to nitroprusside, a vasodilator directly acting on VSMCs, was depressed in patients with migraine (p < 0.001 by analysis of variance). The maximal response of FBF to nitroprusside was 12.1 +/- 2.0 in patients with migraine and 24.1 +/- 1.8 mL x dl(-1) x min(-1) in controls (p < 0.001). During ACh infusion, NO release from the endothelium was similar in patients and controls. In contrast, there was a marked release of cGMP from VSMCs in controls, but not in patients with migraine (-1.9 +/- 2.2 in patients with migraine and -19.1 +/- 5.4 nmol x dL(-1) x min(-1) in controls; p = 0.03). CONCLUSIONS: Patients with migraine are characterized by a distinct vascular smooth muscle cell dysfunction, revealed by impaired cyclic guanosine monophosphate and hemodynamic response to nitric oxide.

Evaluación nutricional de la población infantil Warao en la comunidad de Yakariyene-Estado Delta Amacuro: agosto-octubre 2004 / Evaluation nutritional in of the population infant Warao of the Yakariyene: august-october 2004

Este trabajo tiene como objetivo determinar el estado nutricional de la población infantil de Yakariyene y relacionarla con los resultados positivos del derivado proteico purificado para determinar infección tuberculosa. Estudio de investigación clínica de diseñó descriptivo, transversal con una muestra de 107 niños en edad entre 1 día de nacido y 15 años, que acudieron a la consulta entre agosto y octubre del 2004. Se evaluaron indicadores de dimensión corporal: peso para la edad y talla para la edad circunferencia del brazo izquierdo, siguiendo las tablas de la Organización Mundial de la Salud, se agregó la prueba del derivado proteico purificado. Predominó el sexo masculino 54 por ciento, el mayor porcentaje de pacientes estaba en edad pre escolar 35 por ciento. El 43 por ciento tuvo un resultado de desnutrición 3 por ciento malnutrición en déficit o exceso. El mayor índice de desnutrición se observó en 25 por ciento de los lactantes mayores. 63 por ciento tenía talla normal y 21 por ciento talla baja, el 100 por ciento de la población tenía cicatriz de vacunación y el 45 por ciento de ellos estaban en edad escolar, esto nos demostró que aquellos con PPD positivo 3 por ciento se ubicaban en el grupo etario de lactantes mayores y tenían desnutrición grave. La mayoría de los pacientes tenían una nutrición normal, al destete se presentan los casos de desnutrición, la cobertura de vacunación es buena y no se obtuvieron casos de tuberculosis en la población infantil Warao.

Validación de la prueba nacional de pesquisa de trastornos de desarrollo psicomotor en niños menores de 6 años / Validation for screening test of detecting psychomotor development problems in children under six

Introducción. El uso de una prueba de pesquisa en los primeros años de vida permite la detección temprana de retrasos en el desarrollo psicomotor y su tratamiento oportuno. En la Argentina contamos con una Prueba Nacional de Pesquisa preparada en base a un estudio nacional. El objetivo del trabajo fue validar la prueba, comparando sus resultados con evaluaciones diagnósticas, realizadas en forma simultánea por varios servicios del Hospital Garrahan. Pacientes y métodos. Se seleccionó una muestra de 106 niños de 0 a 5,99 años que concurrían al área de bajo riesgo del Hospital. Se realizaron los siguientes estudios diagnósticos: evaluación del desarrollo psicomotor (Bayley II), examen neurológico, salud mental, coeficiente intelectual (Wechsler, Terman), conducta adaptativa (Vineland), lenguaje (prueba de Gardner receptiva y expresiva, ITPA), audición (emisiones otoacústicas, audiometría tonal, PEAT), examen visual. Se utilizó el DSM-IV como referencia de trastornos del desarrollo. Se evaluó la sensibilidad y especificidad obtenidas según la aplicación de diferentes puntos de corte (número de ítems fracasados). Resultados. El mejor punto de corte se estableció en un ítem tipo A o 2 tipo B, con una sensibilidad del 80%, especificidad: 93%, valor predictivo positivo: 94%, valor predictivo negativo: 77%, porcentaje de coincidencia: 85%. Fue inesperada la elevada prevalencia de problemas de desarrollo encontrada en la muestra: 57%. La prueba es capaz de detectar problemas en las cuatro áreas del desarrollo, incluidos trastornos del lenguaje. Conclusión. Los resultados confirman a la Prueba Nacional de Pesquisa como un instrumento válido para ser usado en el primer nivel de atención para el reconocimiento de niños con sospecha de sufrir trastornos del desarrollo. Asimismo, el trabajo de información permite establecer diferentes puntos de corte y constituye un instrumento útil para su aplicación en la práctica pediátrica.

The use of a screening test in the first years of life allows the early detection of delays of psychomotor development and its treatment, thus contributing to improve the prognosis of the child with special needs. In Argentina, a screening test for detecting developmental problems in children under 6, made with local children and data is available (PRUNAPE). A validation procedure for this test was carried out on 106 children attending at low risk outpatient clinic in Hospital Garrahan. The test was administered to the children together with a battery of diagnostic examinations and studies, performed by experienced specialists from different Hospital services: psychomotor development, neurology examination, mental health, intellectual quotient (Wechsler, Terman), adaptive behaviour (Vineland), language (Gardner expressive and receptive, ITPA), hearing (otoacustic emissions, audiometry, BERA), vision. The DSM ­IV was used as a reference for developmental problems. Using as a failure criterion to the PRUNAPE, the failure of performing correctly one type A item or two type B item, sensitivity of the test was 80%, specificity, 93%; positive predictive value, 95%; negative predictive value, 77%; overall agreement, 85%. A very high prevalence of developmental problems was found: 57%. PRUNAPE was found to be capable of detecting a wide range of problems. These results confirm PRUNAPE as a valuable instrument for early detection of developmental problems in paediatric practice at the primary care level.

A methodological strategy for PAH genotyping in populations with a marked molecular heterogeneity of hyperphenylalaninemia.

The elucidation of the molecular basis of hyperphenylalaninemia in various world populations (PKU Consortium Database: http://www.mcgill/ca/pahdb/) has revealed a remarkable molecular heterogeneity at the locus encoding for phenylalanine hydroxylase. As a consequence, genotyping of HPA patients has prompted the establishment of an impressive number of mutatIon detection protocols. In spite of the large variety of methods proposed so far, no comprehensive strategy has been yet developed for the detection of PAH gene mutations. Therefore, new approaches, combining the advantages of individual methods are required, especially in populations with a high number of PAH gene mutations. In this study, we propose the use of Reverse Dot Blot Analysis within a general mutation protocol to simplify the genotyping of hyperphenylalaninemics in the very heterogeneous population of Sicily (Italy).

In vitro treatment with interleukin-2 normalizes type-1 cytokine production by lymphocytes from elderly.

The term immunosenescence is taken to mean the deterioration of immune function seen in elderly, which is manifested in increased susceptibility to infectious diseases, neoplasias, and autoimmune diseases. It is only recently that we have begun to understand the cellular and molecular changes involved. Of special interest in this regard are observations of a decline in synthesis of Type-1 cytokines which predisposes to diminished cell mediated immunity. We have evaluated the production of type 1 cytokines in old and young donors either in presence or in absence of recombinant interleukin-2 (rIL-2). Lymphocytes were stimulated with plastic bound anti-CD3 and after 48 h the supernatants were harvested and stored at -70 degrees C until assay. Type 1 cytokine, i.e. IL-12 and interferon-gamma (IFN-gamma) production by anti-CD3 stimulated lymphocytes from old subjects was significantly reduced when compared to that from young ones. This impaired production was reversed by adding rIL-2 in the culture medium. In previous studies on aged subjects, we have been able to demonstrate that in vitro treatment with rIL-2 completely restores proliferative responses and partially rescues the increased apoptosis of T cell cultures. Present and previous results suggest that rIL-2 completely restores Type 1 responses by overcoming the well known costimulation deficit of aged lymphocytes.

Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes.

Aging is associated with alterations of the immune system, thought to be related to an increased susceptibility to infectious diseases, and possibly to cancer and autoimmunity in the elderly. In the present paper we report data obtained on freshly collected blood from 148 healthy subjects of different ages (from cord blood to 102 years old). The subjects were divided into seven age classes (cord blood, 3-11 years, 15-39 years, 41-60 years, 61-74 years, 75-84 years, 85-102 years) and their lymphocyte subsets and the expression of the apoptosis-related molecule CD95 were evaluated. In respect of lymphocyte subsets, the major differences were found in the cord-blood samples compared with the oldest old groups. In the cord-blood group, the absolute number of all the lymphocyte subsets was enhanced, but in the oldest group, an increase of CD16+ lymphocytes was observed, whereas CD19+ lymphocytes, which progressively decrease with age, continue to decrease further in the very old. The data show that the expression of CD95 increases until age 74 years, whereas in the oldest old it tends to decrease again. The trend of CD95 expression seems to be related to the change of expression of CD95 on CD4+ lymphocytes, because the CD8+/CD95+ population rose steadily throughout the entire age range. The evaluation of CD95+/CD45R0+ lymphocytes shows similar results to those observed analyzing CD95 on total lymphocytes. Furthermore, a constant increase of CD95+/CD28+ and a related decline of CD28+ lymphocytes was observed in all age groups. These data suggest that the expression of CD95 on the different subsets of lymphocytes can be considered a good marker for studies of immunosenescence, because it may be predictive of successful aging, and can partially explain the change in lymphocytes subsets in elderly.

Trastorno facticio por poder / Factitious disorders by proxy

Un trastorno facticio por poder (TFPP) es una entidad poco frecuente y se caracteriza por la producción o simulación premeditada de signos y síntomas físicos por un perpetrador sobre la persona que se halla a su cargo. El ejemplo extremo es el Síndrome de Munchausen by proxy. La consecuencia es la realización reiterada de consultas, procedimientos diagnósticos y/o terapéuticos, con eventuales daños severos e incluso la muerte. Los signos y síntomas físicos simulados o producidos pueden ser muy diversos. Con el objetivo de describir las características de los niños con TFPP diagnosticados en el Hospital Garrahan se evaluaron 31 historias clínicas entre diciembre/1991 y marzo/1998. Se trata de un trabajo descriptivo y retrospectivo.Se analizaron variables relacionadas con el niño, la forma de presentación y las características del perpetrador y su familia. Se utilizó el método estadísticode Chi cuadrado (programa SPSS 7.5 Windows). El perpetrador fue la madre en el 80.6 por ciento de los casos, el padre en el 6.5 por ciento, ambos en el 9.7 porciento y otros en el 3.2 por ciento. El tiempo medio necesario para el diagnóstico fue de 3.8 meses (1 día a 2.3 años). La edad media del paciente en el momento del diagnóstico fue de 6.4 años (de 7 meses a 14 años). Los motivos de consulta más frecuente fueron: desórdenes gastrointestinales (67.7 por ciento), neurológicos (48.4 por ciento), fiebre (32.2 por ciento), sangrados (28.9 por ciento) ytrastornos infecciosos (12.9 por ciento). El 61.3 por ciento de los pacientes provenía del interior del país, 25.8 por ciento del Gran Buenos Aires y 12.9 por ciento de la Ciudad de Buenos Aires. En el 41.9 por ciento el perpetrador tenía vinculación con la medicina. En el 71 por ciento de los perpetradores se rescataron algunos de los siguientes antecedentes: TFPP, maltrato infantil, drogadicción, depresión o trastorno facticio en el perpetrador. El 67.7 por ciento de los pacientes requirió internación. Se concluye que el TFPP es una patología grave cuyo diagnóstico es difícil y depende del conocimiento de su existencia por parte del médico. Debe ser considerado una forma de maltrato infantil que requiere un abordaje interdisciplinario y debido a su variada forma de presentación, el pediatra debe estar alerta para que dicho trastorno no pase inadvertido.

Interleukin-5 production by mononuclear cells from aged individuals: implication for autoimmunity.

It is well known that in the elderly a deterioration of immune functions may occur. Particularly, stimulation of T cells from aged individuals leads to different kind and/or size of responses if compared with the responses obtained from T cells from young individuals. At the same time, an increase in prevalence of autoantibodies occurs in elderly. The altered production of certain cytokines might explain this paradox of decreased responsiveness to foreign antigens in the face of an increased response to self-antigens. We and others have suggested that this kind of immune response might depend on an age-associated impairment of Th-1 type function that selectively affects production of cytokines involved in the control of cellular responses. In contrast, Th-2 type function is seemingly not affected in elderly, as suggested by normal in vitro production of cytokines involved in humoral responses. To strengthen this hypothesis, in this study we have analysed the influence of age on the ability of mitogen-stimulated cultures of peripheral blood mononuclear cells from human beings to produce another Th-2 type cytokine, i.e. interleukin-5 (IL-5). IL-5 content of both 24- and 48-h stimulated cultures from old individuals was greater than that of young ones, although this difference attained significance only at 48 h. We suggest that the decreased production of Th-1 type cytokines in the presence of a normal or even increased production of Th-2 type cytokines might account for the pattern of immune response which may be observed in elderly, i.e. a normal or increased humoral response, including an autoimmune one, in the face of a low cell mediated immune response.