Optical coherence tomography angiography (OCTA) as a new diagnostic tool in uveitis.

BACKGROUND: The broad spectrum of uveitis disorders requires a multimodal imaging approach in the daily practice of an ophthalmologist. As inflammatory conditions, they have in common an alteration in leukocyte migration. In this context, optical coherence tomography angiography (OCTA) might be of great value for diagnosing or following up patients with these disorders. To date, OCTA has rather been used as an additional tool besides the well-established diagnostic imaging tools, but its complementary diagnostic features become increasingly relevant, to follow disease activity and treatment response and for the understanding of pathomechanisms of various uveitis types. This review summarizes the possible applications of OCTA and its advantages and disadvantages as opposed to dye-based angiographies in uveitic diseases. MAIN BODY: Hitherto gold standards in the diagnostic workup of posterior or intermediate uveitis have been angiography on a dye-based method, which is fluorescein or indocyanine green. It gives information about the status of the blood-retinal barrier and the retinal and choroidal vasculature by visualizing diffuse leakage as a state of inflammation or complications as an ischemia or choroidal neovascularization. As noninvasive methods, fundus autofluorescence depicts the status of metabolic activity of the retinal pigment epithelium and OCT or enhanced depth imaging OCT, respectively, as a depth-resolving imaging method can supply additional information. OCTA as a non-invasive, depth-resolution imaging tool of retinal and choroidal vessels adds detailed qualitative and quantitative information of the status of retinal and choroidal vessels and bridges the gap between the mentioned conventional diagnostic tools used in uveitis. It is important, though, to be aware of its limitations, such as its susceptibility to motion artifacts, limited comparability among different devices, and restricted contribution of information regarding the grade of disease activity. CONCLUSION: OCTA as a non-invasive, depth-resolution imaging tool can give qualitative and quantitative information about the status of retinal and choroidal vessels, but also has certain limitations. Employing OCTA as a complementary rather than exclusive tool, it can give important additional information about the macro- and microvasculature under inflammatory circumstances. Thereby, it also contributes to the understanding of the pathophysiology of various uveitis entities.

Effects of Dietary Acute Tryptophan Depletion (ATD) on NPY Serum Levels in Healthy Adult Humans Whilst Controlling for Methionine Supply-A Pilot Study.

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus.

Studying the effects of dietary body weight-adjusted acute tryptophan depletion on punishment-related behavioral inhibition.

BACKGROUND: Alterations in serotonergic (5-HT) neurotransmission are thought to play a decisive role in affective disorders and impulse control. OBJECTIVE: This study aims to reproduce and extend previous findings on the effects of acute tryptophan depletion (ATD) and subsequently diminished central 5-HT synthesis in a reinforced categorization task using a refined body weight-adjusted depletion protocol. DESIGN: Twenty-four young healthy adults (12 females, mean age [SD]=25.3 [2.1] years) were subjected to a double-blind within-subject crossover design. Each subject was administered both an ATD challenge and a balanced amino acid load (BAL) in two separate sessions in randomized order. Punishment-related behavioral inhibition was assessed using a forced choice go/no-go task that incorporated a variable payoff schedule. RESULTS: Administration of ATD resulted in significant reductions in TRP measured in peripheral blood samples, indicating reductions of TRP influx across the blood-brain barrier and related brain 5-HT synthesis. Overall accuracy and response time performance were improved after ATD administration. The ability to adjust behavioral responses to aversive outcome magnitudes and behavioral adjustments following error contingent punishment remained intact after decreased brain 5-HT synthesis. A previously observed dissociation effect of ATD on punishment-induced inhibition was not observed. CONCLUSIONS: Our results suggest that neurodietary challenges with ATD Moja-De have no detrimental effects on task performance and punishment-related inhibition in healthy adults.

Estudio multicéntrico de deterioro cognitivo en lupus eritematoso sistémico: ECLES / Multicenter study of cognitive decline in systemic lupus erythematousus: ECLES

Introducción: los pacientes lúpicos presentan un riesgo incrementado de deterioro cognitivo (DC) comparado con individuos sanos, el cual puede ser debido a múltiples causas. Objetivo: Describir la frecuencia y características del deterioro cognitivo en pacientes con lupus sin manifestaciones neuropsiquiátricas conocidas. Materiales y método: Se incluyeron pacientes de 16 a 55 años con diagnóstico de LES según criterios del Colegio Americano de Reumatología (ACR) de 1997. Se incluyeron test neuropsicológicos acordes a la propuesta del ACR y el cuestionario de Beck para evaluar depresión. Se definió DC a valores de <2 o más desvíos estándar comparada con la media de población normal en al menos un test. Se consideró focal cuando afectó una o más medidas de un dominio y multifocal en 2 o más dominios. Para comparar proporciones se utilizó prueba exacta de Fisher y para comparar variables numéricas se usó prueba de Kruskal-Wallis. Se consideró significativo un valor de p <0,05. Resultados: Se estudiaron 86 pacientes con lupus, el 90% de origen caucásico, 8% mestizos y 1% amerindio. El 82% alcanzó nivel secundario. La frecuencia de DC fue del 65% (56/86). Los dominios afectados: memoria 45%, funciones ejecutivas 30%, atención 29%, lenguaje 4,6%. Se detectó depresión en un 48% de los pacientes. Se analizaron diferentes factores de riesgo, sin hallar diferencias estadísticamente significativas a excepción de la etnia (p=0,02). Conclusión: Se halló una frecuencia elevada de deterioro cognitivo en pacientes con LES, los pacientes no caucásicos tuvieron mayor DC con diferencias significativas en comparación con los pacientes caucásicos.

Background: patients with systemic lupus erythematosus (SLE)have an increased risk of cognitive impairment (CI) compared tohealthy individuals and it may be due to multiple causes. Objective: To determine the frequency and characteristics of CI inlupus patients without known previous neuropsychiatric events. Methods: Patients aged 16 to 55 fulfilling the 1997 ACR criteria forSLE were included. The neuropsychological test battery proposedby the ACR was used to determine CI and Beck depression werealso assessed. CI was defined as values of ≤2 standard deviationscompared to the mean of the general population in at least one test. It was considered focal involvement if it affected one or more measuresof a single domain and multifocal if 2 or more domains wasaffected. To compare proportions, Fisher’s exact test was used andto compare numerical variables, Kruskal-Wallis. A value of p <0.05was considered significant. Results: 86 patients were evaluated, 90% were Caucasian, 8%mestizos and 1% Amerindian. 82% had high school. CI was foundin 65% of patients (56/86). The affected domains were: memory45%, executive functions 30%, attention 29% and language 4.6%. Depression was detected in 48% of patients. Different risk factorswere analyzed and found no statistically significant differences exceptfor ethnicity (p=0.02). Conclusion: A high frequency of CI was found in patients with SLE,non-Caucasian had higher CI with significant differences in comparisonwith Caucasian patients.

Elastofibroma dorsi: clinicopathological analysis of 71 cases.

INTRODUCTION: Elastofibroma dorsi (ELD) is a rare soft tissue benign tumor of the chest wall. So far, only a few large series have been reported in the English literature and, to the best of our knowledge, radiological assessment and clinical management remain without consensus. The aim of this study is to provide, on the basis of a single-institutional, homogeneous and large experience, ample evidences to support etiological and "clinical-usefulness-grade" classification hypotheses. MATERIALS AND METHODS: We report observational information on 71 ELD cases and, on the basis of these, we discuss the clinical onset features, radiological and surgical characteristics, as well as pathological and immunohistochemical evidences. RESULTS: In the period between January 1994 and September 2009, 71 consecutive patients (23 male and 48 female; mean age: 60.2 years; standard deviation [SD] ± 8.3 years) with ELD diagnosis were surgically treated at our institution. ELD was right sided in 34 patients (47.9%), left in 25 (35.2%), and bilateral in 12 (16.9%). In nine patients, ELD were diagnosed synchronously and three metachronously. Thirty-eight patients (53.5%) had no significant symptoms; 33 (46.5%) reported a clunking sensation or a localized scapular swelling during the shoulder movements. Sixty-six (93%) patients underwent surgical excision with radical intent while in five patients, a biopsy-only procedure was undertaken. Mean hospital stay was 3.0 days (SD ± 1.2 days) with a morbidity of 10.6% (one case of major postoperative bleeding requested a surgical revision of the hemostasis). At the univariate analysis, the probability of occurrence of morbidity increases with tumor size. All operated patients are alive and well at follow-up with no sign of recurrence and complete resolution of the symptomatology. CONCLUSIONS: ELD is relatively uncommon, benign, and well controlled by radical surgery.

[Clinical effect of bovine pericardial strips on air leak after stapled pulmonary resection in "frail" patients: early results]. / Impiego clinico di suturatrici rivestite con pericadio bovino nella prevenzione delle perdite aeree postoperatorie in pazienti "fragili" sottoposti a resezione polmonare.

AIM: Postoperative air leaks and in particular persistent air leaks (>5 days) after pulmonary resection still represent a common complication and the first cause of hospital stay delay. Aim of this experimental trial was to investigate the efficacy of the use of bovine pericardium strips (in terms of reduction of postoperative leakage and hospital stay) in "critical" patients (COPD, emphysema etc.) who underwent pulmonary resection. METHODS: From October 2010 to February 2011, eight patients (experimental group, Group A) were preoperative selected and underwent pulmonary resection with bovine pericardium strips (Peri-Strips Dry; Synovis ). The inclusion criteria of a "frail patient" were established by a dedicate pneumologist according with clinical and functional data (predicted postoperative FEV1 ranging from 35% and 80% of the theorical predicted value). For comparison, from January 2010 to September 2010, we retrospectively reviewed the data of 28 patients who satisfied the same inclusion criteria and underwent pulmonary resection with standard surgical procedures. This group of patients represents our control group (Group B). RESULTS: There were no significant differences between the two groups in age, gender, preoperative risk factors for developing a postoperative air leak, preop FEV1 and type of resection. No technical deficiencies in the use of bovine pericardium strips were observed in Group A. Postoperative leakage was significant different in the two groups being persistent air leak detected in 0% in Group A versus 17.8% of Group B (P=0.046). Consequently, chest tube duration (6.75±0.84 days [Group A] vs. 9.70±1.26 days (Group B), P=0.019) and hospital stay (10.13±0.83 days [Group A] vs. 12.95±1.37 days [Group B], P=0.013) were lower in the experimental group. CONCLUSION: Bovine pericardium strips are safe and easy-to-do technique to reduce postoperative air leaks after pulmonary resection in "critical" patients.

Huge primary pericardial liposarcoma.

Liposarcomas are the second most common soft tissue sarcoma in adults. They occur predominantly in the lower limbs and retroperitoneum, whereas primary mediastinal liposarcomas are extremely rare. Liposarcomas are often asymptomatic and may reach a considerable size before causing any symptoms related to direct invasion or compression of other thoracic organs. We report a case of a 69-year-old woman with a giant primary pericardial liposarcoma causing cardiac tamponade and discuss its clinical and imaging features and surgical treatment and review the literature.

Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia.

Hearing impairment is one of the most common disorders of sensorineural function and the incidence of profound prelingual deafness is about 1 per 1000 at birth. GJB2 gene mutations make the largest contribution to hereditary hearing impairment. The spectrum and prevalence of some GJB2 mutations are known to be dependent on the ethnic origin of the population. This study presents data on the carrier frequencies of major GJB2 mutations, c.35delG, c.167delT and c.235delC, among 2308 healthy persons from 18 various populations of Eurasia: Russians, Bashkirs, Tatars, Chuvashes, Udmurts, Komi-Permyaks and Mordvins (Volga-Ural region of Russia); Belarusians and Ukrainians (East Europe); Abkhazians, Avars, Cherkessians and Ingushes (Caucasus); Kazakhs, Uighurs and Uzbeks (Central Asia); and Yakuts and Altaians (Siberia). The data on c.35delG and c.235delC mutation prevalence in the studied ethnic groups can be used to investigate the prospective founder effect in the origin and prevalence of these mutations in Eurasia and consequently in populations around the world.

An STR database on the Volga-Ural population.

This work develops a reference STR database on the Volga-Ural population, Russia, comprised of 640 individuals that were sampled from eight ethnic groups (Finno-Ugric Mari, Mordva-Moksha, Mordva-Erzja, Komi-Permjak, and Udmurt, and Turkic-speaking Bashkir, Tatar-Mishary, and Chuvash) and typed with 10 autosomal STR markers: TH01, CSF1P0, FGA, vWA, D3S1358, TPOX, D16S539, D8S1179, D13S317, FES. The groups differentiate in allele frequencies, and therefore we computed theta-values between allele frequencies in each ethnic groups and those in the database as a measure of their differentiation. Nevertheless, the Volga-Ural ethnic groups form a relatively compact cluster that greatly deviate from the Romanic Moldovans and the Turkic Yakuts, taken for comparison, and are closer to the Slavic Russians, Belarusians, and Ukrainians, although significantly differ from those as well.

Treatment of central venous catheter fungal infection using liposomal amphotericin-B lock therapy.

The current standard of care for a fungal central venous catheter infection in a pediatric patient usually requires removal without any other feasible options. Although removal may reduce the rate of Candida-associated complications, literature reviews question whether the outcomes of removal substantiate this being the standard of care. We report 6 cases of central venous catheter fungal infections treated with liposomal amphotericin-B lock therapy. These cases consisted of 4 patients, 2 of whom received recurrent therapy. In 4 of these cases, there was successful eradication of the infectious fungal agent, allowing continued use of the catheter. A controlled study of antifungal lock therapy should be considered as a potential alternative to removal.

Cognitive deficits in multiple sclerosis correlate with changes in fronto-subcortical tracts.

Cognitive function and diffusion tensor imaging were assessed in a group of 12 patients with early relapsing-remitting multiple sclerosis (disease duration

Virtual musculo-skeletal model for the biomechanical analysis of the upper limb.

In this paper, a musculo-skeletal model of the upper limb is presented. The limb is modelled as a three-dimensional 7 degrees-of-freedom system, linked to the shoulder, which has been considered as frame. The upper limb model is made up of four links corresponding to the most important body segments: the humerus, the ulna, the radius and the hand, considered as a single rigid body. Particular attention has been paid to the modelling of joints in order to mimic all the possible arm and forearm movements (including prono-supination). The model also includes 24 muscles. The mathematical model used to describe the muscles is that proposed by Zajac in 1989, modified by the authors. The kinematic analysis has been performed including an ergonomics index to take into account the posture and joint physical limits. Moreover an optimization criterion based on minimum activation pattern has been included in order to find muscular activation coefficients. The results of the proposed methodology concerning muscular activations have been compared to those coming from processed EMG signals, which have been acquired during experimental tests.

Quantitative expression of the major homing integrins alphaL and alpha4 on human cord blood hematopoietic progenitor and stem cells.

An increased traffic of hematopoietic progenitor cells (HPC) between bone marrow and peripheral organs is a peculiar feature of the allergic inflammation. It has been recently reported that the sublingual form of specific immunotherapy (SLIT) is capable of reducing such an increased HPC traffic. The House Dust Mite major antigen Der p1 has been proved to up-regulate the expression of the ICAM-1 and VCAM-1 endothelial addressins, supporting the view of an inflammatory cell recruiting at the site of allergen extract administration. In the present work we have investigated, by flow-cytometric techniques, the expression of the two major integrins CD11a (LFA-1) and CD49d (VLA-4) that are the homing receptor cognate for ICAM-1 and VCAM-1 on human cord blood CD34 hematopoietic progenitor and stem cells. Even if both the investigated molecules resulted detectable on CD34+ HPC surfaces, being the system redundant, the density of the cellular expression was significantly higher for CD49d (median value: 158) than CD11a (median value: 20.5), suggesting a preferential usage of the homing axis VLA-4/VCAM-1. Results consistency with outcomes of clinical trials that relate SLIT efficacy to allergen dosage is discussed.

Mite antigens enhance ICAM-1 and induce VCAM-1 expression on human umbilical vein endothelium.

Although sublingual allergen-specific immunotherapy has been proved to be effective in the treatment of allergic diseases, controversy surrounds the means by which such a local therapy can induce systemic immunological changes. Adhesion molecules are critical in the regulation of leukocyte traffic. It has been hypothesized that allergenic extract, administered locally, may induce an up-regulation of the mucosal vessel vascular adhesion molecules (CAMs) resulting in local recruitment of circulating inflammatory cells. In the present study we investigated whether the mite antigens, Der p1 and Der p2, can modulate CAM expression of human endothelial cells (HEC). To do this, slices of whole human umbilical cord vein underwent short-term (8 hours) cultures in the presence or absence of mite antigen (baseline, unstimulated controls). Cryostatic sections of the specimens were then evaluated immunohistochemically for expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) molecules. The results revealed that while Der p1 is capable of significantly up-regulating ICAM-1 and VCAM-1 on HEC, Der p2 antigen moderately up-regulates ICAM-1 expression but is ineffective in modulating VCAM-1. Although preliminary, these results clearly support the hypothesis that at least some of the effects of sublingual immunotherapy may derive from inflammatory cell recruitment at the site of allergen release.

Mite antigens enhance ICAM-1 and induce VCAM-1 expression on Human Umbilical Vein Endothelium

Although sublingual allergen-specific immunotherapy has been proved to be effective in the treatment of allergic diseases, controversy surrounds the means by which such a local therapy can induce systemic immunological changes. Adhesion molecules are critical in the regulation of leukocyte traffic. It has been hypothesized that allergenic extract, administered locally, may induce an up-regulation of the mucosal vessel vascular adhesion molecules (CAMs) resulting in local recruitment of circulating inflammatory cells. In the present study we investigated whether the mite antigens, Der p1 and Der p2, can modulate CAM expression of human endothelial cells (HEC). To do this, slices of whole human umbilical cord vein underwent short-term (8 hours) cultures in the presence or absence of mite antigen (baseline, unstimulated controls). Cryostatic sections of the specimens were then evaluated immunohistochemically for expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) molecules. The results revealed that while Der p1 is capable of significantly up-regulating ICAM-1 and VCAM-1 on HEC, Der p2 antigen moderately up-regulates ICAM-1 expression but is ineffective in modulating VCAM-1. Although preliminary, these results clearly support the hypothesis that at least some of the effects of sublingual immunotherapy may derive from inflammatory cell recruitment at the site of allergen release (AU)

Aunque se ha demostrado que la inmunoterapia sublingual con alergeno específico (ITSA) es eficaz en el tratamiento de enfermedades alérgicas, se discute cómo un tratamiento local puede inducir modificaciones inmunitarias sistémicas. Las moléculas de adhesión son esenciales en la regulación leucocitaria, y se ha planteado la hipótesis de que el extracto alergénico, administrado localmente, puede inducir una estimulación de las moléculas de adhesión vascular (CAM) de los vasos de la mucosa, que se traduce en un reclutamiento local de células inflamatorias circulantes. En el presente trabajo hemos investigado si los antígenos de ácaros Der p1 y Der p2 pueden regular la expresión de células endoteliales humanas (CEH) por CAM. Para ello, se sometió a cortes de vena de cordón umbilical humano completo a cultivos a corto plazo (8 horas) en presencia o en ausencia del antígeno de ácaro (controles no estimulados basales). Después se evaluó inmunohistoquímicamente la expresión de moléculas ICAM-1 y VCAM-1 en cortes criostáticos de las muestras. Este análisis reveló que Der p1 es capaz de regular significativamente ICAM-1 y VCAM-1 sobre CEH, mientras que el antígeno Der p2 regula moderadamente la expresión de ICAM-1 pero es ineficaz para regular VCAM-1. Un que preliminares, estos resultados apoyan conclaridad la hipótesis de que al menos parte de los efectos de la inmunoterapia sublingual pueden deberse al reclutamiento de células inflamatorias en el lugar de liberación del alergeno (AU)

CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation.

BACKGROUND: There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. METHOD: We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. RESULTS: CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). CONCLUSIONS: The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation.

CD34+ cells in peripheral blood of healthy human beings and allergic subjects: clue to acute and minimal persistent inflammation

Background: There is compelling evidence that hemopoietic precursor cells (HPC) play a crucial role in establishing cellular inflammation in allergic diseases. Increased levels of circulating CD34+ HPC committed to the myeloid lineage have been extensively reported in allergic rhinitis, asthma and eczema, whereas CD34+ cells have been identified within the cellular infiltrates of tissues, at peripheral sites of inflammation. Method: We conducted a pilot study to evaluate CD34+ traffic in the peripheral blood of 22 consecutive patients (13 men and nine women; mean age 28.9 years), independently of treatment. The patients presented rhinitis, asthma, eczema, urticaria and adverse food reactions of suspected allergic origin. Allergic reactions were extrinsic in 18 patients and intrinsic in four. In 12 patients who underwent sublingual specific immunotherapy, CD34+ cells were quantified at enrollment (T0), one year later (T1) and two years later (T2). The severity of symptoms was graded on a five-point scale (0 = absence of symptoms and 4 = severe symptoms). Twenty healthy human subjects (10 men and 10 women; mean age 24.5 years) were evaluated as controls. To obtain information about the total amount of circulating HPC, independently of the lineage commitment (Lin+/-) and the degree of differentiation (CD34bright/dim), we used a modification of the Milan protocol of peripheral blood CD34+ cell estimation. The cells were analyzed using a BD FACScan or FACSCalibur and the results were expressed as the percentage of positive cells. Results: CD34+ cell traffic in the control group was very low since all values were < 0.10 (median value: 0.03 %). Values in the patient group were increased in both extrinsic and intrinsic forms with a median value of 0.25 % (interquartile range: 0.13- 0.33 %). The relationship between CD34+ traffic and the severity score was highly significant (Spearman's rho = 0.954; test of Ho: CD34; independent score: Pr > t = 0.000). Conclusions: The data reported herein suggest that the method employed is effective in assessing acute allergic inflammation, as well as minimal persistent inflammation underlying an asymptomatic clinical condition. Evaluation of CD34bright/dim peripheral traffic, if confirmed by the outcomes of a multicenter study currently being planned together with traditional study of circulating IgE, could be a reliable non-invasive laboratory tool for monitoring allergic inflammation (AU)

Antecedentes: Existen datos convincentes de que las células precursoras hematopoyéticas (HPC) desempeñan una función esencial en el establecimiento de la inflamación celular en las enfermedades alérgicas. Se han descrito a menudo mayores concentraciones de CD34+ HPC circulantes, comprometidas con la estirpe mieloide, en la rinitis alérgica, el asma y el eccema, mientras que se han identificado células CD34+ en los infiltrados celulares de tejidos, en zonas periféricas de inflamación. Método: Realizamos un estudio preliminar para evaluar el tráfico de CD34+ en la sangre periférica de 22 pacientes consecutivos (13 varones y 9 mujeres; promedio de edad de 28,9 años), con independencia del tratamiento. Los pacientes padecían rinitis, asma, eccema, urticaria y reacciones alimentarias adversas de presunto origen alérgico. Las reacciones alérgicas eran extrínsecas en 18 pacientes e intrínsecas en cuatro. En el caso de 12 pacientes que recibieron inmunoterapia específica por vía sublingual se cuantificaron las células CD 34 + en el momento de inscripción (T0), un año después (T1) y dos años más tarde (T2). La intensidad de los síntomas se graduó con una escala de cinco puntos (0 = ausencia de síntomas y 4 = síntomas graves). Se evaluó como testigos a 20 personas sanas (10 varones y 10 mujeres; promedio de edad de 24,5 años).Para obtener información sobre la cantidad de HPC circulantes, con independencia del compromiso de estirpe (Lin ñ ) y el grado de diferenciación (CD34bright/dim: no divididas/divididas), aplicamos una modificación del protocolo de Milán para calcular las células CD34+ en sangre periférica. Las células se analizaron empleando un BD FACScan o un FACSCalibur y los resultados se expresaron como porcentaje de células positivas. Resultados: El tráfico de células CD 34 + en el grupo de control fue muy escaso, pues todos los valores fueron t = 0,000].Conclusiones: Los datos descritos indican que el método empleado es eficaz para evaluar la inflamación alérgica aguda, así como la inflamación persistente mínima que subyace a una enfermedad clínica asintomática. La evaluación del tráfico periférico de CD34bright/dim, si lo confirman los resultados de un estudio multicéntrico que se está planificando junto con un estudio tradicional de la IgE circulante, podría ser un método de laboratorio incruento fidedigno para vigilar la inflamación alérgica. (AU)

Recovery of hematopoietic activity in bone marrow from human immunodeficiency virus type 1-infected patients during highly active antiretroviral therapy.

The mechanisms responsible for the hematopoietic failure in human immunodeficiency virus type 1 (HIV-1)-infected patients are still unknown. Several findings indicate that the in vitro proliferative potential of precursor cells from AIDS patients is reduced. The changes seen in bone marrow (BM) morphology and the defective BM functions associated with cytopenias have both been proposed as potential explanations. In patients treated with highly active antiretroviral therapy (HAART) an immune reconstitution associated with increased whole blood cell counts has been described. We have investigated the effects of HAART on the number of colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs), using long-term BM cell cultures (LTBMC) in a group of subjects with HIV-1 infection enrolled in an open study to evaluate the mechanisms of immune reconstitution during HAART. In each patient, the increase in colony growth was homogeneous, regardless of the type of hematopoietic progenitor cells assayed; in four subjects an increase in the most primitive progenitor cells (LTC-ICs) was observed. These findings were associated with the in vivo data showing increased numbers of BM mononuclear cells (BMMCs) after HAART and with a rise in peripheral CD4(+) T cell counts and decreased levels of plasma HIV-1 RNA. A decreased number of hematopoietic progenitor cells and/or a defective modulation of progenitor cell growth might be the cause of the hematological abnormalities in AIDS patients. Controlling HIV-1 replication by HAART could determine a restoration of stem cell activity, probably because of the suppression of factors that inhibit normal hematopoiesis.

Brainstem regions with neuronal activity patterns correlated with priming of locomotor stepping in the anesthetized rat.

Locomotor stimulation in the perifornical hypothalamus produces a transient facilitation of subsequent locomotion, a priming effect, such that stepping to a second train of stimulation occurs with a shorter latency of onset and increased amplitude. Neurons responsible for the initiation of this facilitated stepping presumably respond to locomotor stimulation with a similar priming effect, i.e. either a shorter latency or a larger change in activity rate. This study used anesthetized rats (urethane, 800mg/kg) to compare brainstem regions in terms of the relative rates of occurrence of single neurons that showed both specific responses to locomotor stimulation and also priming effects. Specific responses were characterized by a progressive increase in activity prior to the first step (a Type I pattern). In that they co-varied in time with the increased probability of stepping onset, Type I responses were more specific than Type II responses, which peaked early in the stimulation train several seconds before the onset of stepping. Regions with high proportions of neurons showing Type I responses and priming effects included the anterior dorsal tegmentum lateral to the central gray, the oral pontine reticular nucleus and the medial gigantocellular nucleus. Few Type I neurons showed a modulation of activity related to the step cycle. Type I primed neurons were uncommon in the cuneiform and the pedunculopontine regions, but neurons showing other patterns (decreases and antidromic responses) were relatively prevalent there. The ventral tegmental area was generally unresponsive. The results indicate that stepping elicited by perifornical stimulation in the anesthetized rat is mediated by circuits that differ at midbrain levels from the circuits implicated in other types of locomotion. Two regions, the anterior dorsal tegmentum and the oral pontine reticular nucleus, warrant further attention to determine their possible roles in the initiation of locomotion.

Fast and accurate edge-based segmentation with no contour smoothing in 2-D real images.

In this paper we propose an edge-based segmentation algorithm built on a new type of active contour which is fast, has a low computational complexity and does not introduce unwanted smoothing on the retrieved contours. The contours are always returned as closed chains of points, resulting in a very useful base for subsequent shape representation techniques.