Beyond brain injury biomarkers: chemoattractants and circulating progenitor cells as biomarkers of endogenous rehabilitation effort in preterm neonates with encephalopathy.

Introduction: Preclinical work and studies in adults have shown that endogenous regeneration efforts that involve mobilization of progenitor cells take place after brain injury. However, kinetics of endogenous circulating progenitor cells (CPCs) in preterm neonates is not well described, particularly their possible role regarding brain injury and regeneration. We aimed to assess the kinetics of CPCs in neonates with encephalopathy of prematurity in relation to brain injury biomarkers, chemoattractants and relevant antenatal and postanal clinical factors, in an effort to outline the related pathophysiology. Materials and methods: 47 preterm neonates (of 28-33 weeks GA) were enrolled: 31 newborns with no or minimal brain injury (grade I IVH) and 16 prematures with encephalopathy (grade III or IV IVH, PVL or infarct). Peripheral blood samples obtained on days 1, 3, 9, 18 and 45 after birth were analyzed using flow cytometry, focusing on EPCs (early and late Endothelial Progenitor Cells), HSCs (Hematopoietic Stem Cells) and VSELs (Very Small Embryonic-Like Stem Cells). At the same time-points serum levels of S100B, Neuron-specific Enolase (NSE), Erythropoietin (EPO), Insulin-like growth factor-1 (IGF-1) and SDF-1 were also measured. Neonates were assessed postnatally with brain MRI, and with Bayley III developmental test at 2 years of corrected age. Results: Preterms with brain injury proved to have significant increase of S100B and NSE, followed by increase of EPO and enhanced mobilization mainly of HSCs, eEPCs and lEPCs. IGF-1 was rather decreased in this group of neonates. IGF-1 and most CPCs were intense decreased in cases of antenatal or postnatal inflammation. S100B and NSE correlated with neuroimaging and language scale in Bayley III test, providing good prognostic ability. Conclusion: The observed pattern of CPCs' mobilization and its association with neurotrophic factors following preterm brain injury indicate the existence of an endogenous brain regeneration process. Kinetics of different biomarkers and associations with clinical factors contribute to the understanding of the related pathophysiology and might help to early discriminate neonates with adverse outcome. Timely appropriate enhancement of the endogenous regeneration effort, when it is suppressed and insufficient, using neurotrophic factors and exogenous progenitor cells might be a powerful therapeutic strategy in the future to restore brain damage and improve the neurodevelopmental outcome in premature infants with brain injury.

Mobilization of circulating progenitor cells following brain injury in premature neonates could be indicative of an endogenous repair process. A pilot study.

BACKGROUND: Preclinical data and adult studies have showed an endogenous regeneration process following brain damage that involves mobilization of progenitor cells. This process is not well described in preterm neonates. The present study aims to investigate the mobilization of Circulating Progenitor Cells (CPCs) and their relation to biomarkers of brain injury in preterm neonates. METHODS: This is a prospective cohort study of preterm infants with gestational age (GA) <34 weeks. Serial cranial ultrasounds scans were performed in all neonates. Brain injury was defined by the presence of intraventricular hemorrhage grade III/IV, cystic periventricular leukomalacia or infarct. Peripheral blood samples were collected from all neonates on days(d) 1, 3, 9, 18 and 45 of life for the measurement of levels of CPCs [early and late Endothelial Progenitor Cells (EPCs), Haematopoietic Stem Cells (HSCs) and Very Small Embryonic-Like Stem Cells (VSELs)], Neuron-Specific Enolase (NSE), S100b, Erythropoietin (EPO) and Stromal Cell-Derived Factor-1 (SDF-1) . RESULTS: Ten out of the 23 preterm infants included in the study developed brain injury; the remaining thirteen infants served as controls. In the brain injury group a significant increase of HSCs (d9, d45), early EPCs (d3, d9, d18) and late EPCs (d1, d3, d9, d18, d45) was observed compared to controls. VSELs on d45 were significantly higher in controls. S100b on d1, EPO on d1, SDF-1 on d3 and NSE on d18 were significantly increased in the brain injury group. Moreover, CPCs were significantly related to S100b, NSE, EPO and SDF-1 levels at multiple time points. CONCLUSIONS: The observed pattern of CPCs mobilization and its association with biomarkers following brain injury in preterm neonates indicate the existence of an endogenous brain regeneration process. Enhancement of this process with exogenous progenitor cell transplantation might be a powerful therapeutic strategy to restore brain damage and improve the neurodevelopmental outcome in premature infants. Hippokratia 2015; 19 (2):141-147.

Levels of inflammatory mediators in chronic obstructive pulmonary disease patients with anemia of chronic disease: a case-control study.

BACKGROUND: Although a subset of patients with chronic obstructive pulmonary disease (COPD) display anemia, the role of elevated pro-inflammatory cytokines in COPD-related anemia of chronic disease (ACD) has not been fully investigated. AIM: To examine the levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), C-reactive protein (CRP) and erythropoietin in stable COPD outpatients with and without ACD. DESIGN: A case-control design was followed. METHODS: Fifty-four patients with stable COPD were studied. Among them, 27 had ACD according to strict clinical and laboratory criteria (group of cases), while another 27 nonanemic COPD patients, carefully matched to cases for age, gender, height, lung function and smoking status represented the controls. Serum levels of IL-1ß, IL-6, IL-10, TNFα, IFNγ, CRP and erythropoietin were measured in both groups. RESULTS: Patients with ACD had significantly higher levels of IL-10 [25.6 (1.9-95.2) vs. 4.1 (1.9-31.9) pg/ml, P = 0.049] and IFNγ [15.2 (2.2-106.9) vs. 2 (1.2-18.3) pg/ml, P = 0.026] and had more frequently elevated CRP than controls. Levels of IL-1ß [26.2 (9.8-96.4) vs. 7.9 (2.1-28.4) pg/ml, P = 0.073], IL-6 [20.3 (2.1-125.4) vs. 6.2 (1.2-33.8) pg/ml, P = 0.688] and TNFα [30.1 (3.2-107.5) vs. 10.1 (3.2-50.4) pg/ml, P = 0.131] were also higher in cases, but the differences did not reach statistical significance. Patients with ACD also displayed significantly higher erythropoietin levels than controls [(21.9 (8.4-101.7) vs. 9.7 (6.3-21.7) mIU/ml, P = 0.010], indicating erythropoietin resistance. CONCLUSION: This study shows that in stable COPD outpatients with strictly defined ACD, levels of inflammatory mediators and erythropoietin are elevated compared to nonanemic controls.

Bronchoalveolar lavage fluid eosinophils are correlated to natural killer cells in eosinophilic pneumonias.

BACKGROUND: Eosinophilic lung diseases comprise a group of heterogeneous pulmonary disorders linked by increased eosinophils in bronchoalveolar lavage fluid (BALF). There is supporting evidence that natural killer (NK) cells participate in the regulation of eosinophilic inflammation. OBJECTIVE: Our aim was to investigate the relationship between eosinophils and NK cells in BALF in patients with different interstitial lung diseases (ILDs) focusing on eosinophilic pneumonias. METHODS: Of 114 patients who presented with increased BALF eosinophils (>5%), 74 patients were classified into the following groups: 27 had eosinophilic pneumonia (EP), 17 had idiopathic pulmonary fibrosis (IPF), 16 had hypersensitivity pneumonitis (HSP) and 14 had cryptogenic organizing pneumonia (COP/BOOP). Total BALF cells, cell density and cell differential counts were assessed and lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK) and CD3+CD16/56+ (NKT) were determined by flow cytometry. RESULTS: Significant differences were observed in the percentages of lymphocytes (p < 0.001) and CD3+CD16/56+ cells (p = 0.023) among patient groups. In patients with EP, the percentage of eosinophils correlated positively with the number of CD3-CD16/56+ cells (r = 0.522, p = 0.005), the percentage of CD3-CD16/56+ cells (r = 0.690, p < 0.001), and the absolute count of CD3+CD16/56+ absolute cells (r = 0.609, p = 0.001). However, in patients with IPF, HSP or COP/BOOP, no correlation between the percentage of eosinophils and CD3-CD16/56+ or CD3+CD16/56+ cells was observed. CONCLUSIONS: Eosinophil inflammation seems to develop through a different pathway in EP compared to other ILDs.

Leptin responses to long-term cardiorespiratory exercise training without concomitant weight loss: a prospective study.

AIM: The aims of the present study were to examine 1) whether changes in circulating leptin levels occur in response to six months of aerobic exercise training (ET) without concomitant weight loss; 2) whether there is a different response with respect to gender; and 3) the relationship between age and leptin and whether this relationship has any impact on the response to ET without weight-loss. METHODS: Thirty-eight healthy, sedentary men and women (age 38.43+/-2.24, range 18-59 years) participated in 6 months of supervised, moderate intensity (ET) performed 4 days per week. Maintenance of usual dietary practices were encouraged to minimize weight-loss. Participants were evaluated for circulating fasting leptin, body mass, body fat percentage and maximal aerobic power (VO2max) prior to and after ET. RESULTS: There was no decrease in body weight or leptin concentration (17.69+/-2.67 vs 16.85+/-3.12 ng dL(-1)). Gender did not affect the response to exercise training. The bivariate correlation between leptin and age was not significant, but the relationship reached significance after controlling for body fat percentage and VO2max (r = -0.358, P < 0.05). Age did not affect the response of leptin concentration to ET. CONCLUSION: It is probable that changes in leptin concentration reported previously with ET may be attributable to concomitant weight loss, but age does not play a role in how leptin responds to ET.

[Immune factors or depression? Fatigue correlates in Parkinson's disease]. / Factores inmunes o depresión? La fatiga relacionada con la enfermedad de Parkinson.

INTRODUCTION: Fatigue is a frequent symptom in Parkinson disease (PD), but its pathogenesis remains obscure. Fatigue may be influenced by depression and motor disability, but immunological factors have been also implicated. The purpose of the study was to assess fatigue in PD patients in relation to depression and various immunological factors. SUBJECTS AND METHODS: Forty PD patients and 26 normal matched controls were studied. Fatigue was assessed by the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for depression screening. The following immunological factors were estimated: a) T- and B-lymphocytes, T-lymphocyte subsets (helper/suppressor cells) as well as natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL-1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha. RESULTS: FSS mean score was higher in PD patients compared to controls (p < 0.01). Significant differences between patients and controls were found in the following immunological parameters. In PD patients: a) mean percentage of NK cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p < 0.01) and IL-1Ra levels were decreased (p < 0.001). FSS correlated significantly to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p < 0.01), but after exclusion of depressed PD subjects this correlation significance level dropped to p = 0.055. CONCLUSIONS: Our results indicate that fatigue is a common non motor symptom in PD. Immunological differences between PD patients and controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood levels. Fatigue correlated to depression and IL-Ra levels. However after exclusion of depressed subjects IL-1Ra levels showed only a tendency to significance, leaving depression as the principle correlate of fatigue.

¿Factores inmunes o depresión? La fatiga relacionada con la enfermedad de Parkinson / Immune factors or depression? Fatigue correlates in parkinson’s disease

La fatiga es un síntoma frecuente en la enfermedad de Parkinson (EP), pero su patogénesis permanecesin aclarar. El propósito de este estudio fue evaluar la fatiga de pacientes con EP en relación con los factores inmunológicos.Sujetos y métodos. Se estudiaron 40 pacientes con EP y 26 sujetos control. La fatiga se evaluó con la Fatigue SeverityScale (FSS). Se empleó el Beck Depression Inventory (BDI) para examinar la depresión. Como factores inmunológicos se estudiaron los linfocitos T y B, subclases de linfocitos T (helper y supressor), así como las células natural killer (NK), y los nivelessanguíneos de interleucinas IL-1alfa, IL-1beta, IL-6, el antagonista del receptor de IL-1 (IL-1Ra) y el factor de necrosis tumoral alfa. Resultados. Se encontró significación estadística (p < 0,01) entre los niveles sanguíneos de IL-1Ra y la gravedad de la fatiga, pero tras excluir los pacientes con depresión y EP, el nivel de significación disminuyó a p = 0,055. Conclusiones.Se hallaron diferencias inmunológicas en los niveles sanguíneos de pacientes con EP y sujetos control en los porcentajes de células NK, IL-1beta e IL-1Ra. La fatiga correlacionaba con la depresión y los niveles de IL-1Ra. Sin embargo, tras la exclusión de los pacientes con depresión, los niveles de IL-1Ra mostraron sólo una tendencia hacia la significación, y situarona la depresión como el principal factor correlacionado con la fatiga

Fatigue is a frequent symptom in Parkinson disease (PD), but its pathogenesis remains obscure.Fatigue may be influenced by depression and motor disability, but immunological factors have been also implicated. The purpose of the study was to assess fatigue in PD patients in relation to depression and various immunological factors.Subjects and methods. Forty PD patients and 26 normal matched controls were studied. Fatigue was assessed by the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for depression screening. The following immunological factors were estimated: a) T-and B-lymphocytes, T-lymphocyte subset(helper/suppressor cells) as well as natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL-1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) andtumor necrosis factor-alpha. Results. FSS mean score was higher in PD patients compared to controls (p < 0.01). Significant differences between patients and controls were found in the following immunological parameters. In PD patients: a) mean percentage of NK cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p < 0.01) and IL-1Ra levels weredecreased (p < 0.001). FSS correlated significantly to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p < 0.01), but after exclusion of depressed PD subjects this correlation significance level dropped to p = 0.055. Conclusions.Our results indicate that fatigue is a common non motor symptom in PD. Immunological differences between PD patients and controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood levels. Fatigue correlated to depression and IL-Ra levels. However after exclusion of depressed subjects IL-1Ra levels showed only a tendency to significance, leaving depression as the principle correlate of fatigue

Respiratory effects in workers processing dried tobacco leaves.

OBJECTIVES: The aim of this study was to examine the pollution level of the occupational environment and to investigate the effects of occupational exposure to tobacco dust on the respiratory system of tobacco workers. No such study has previously been conducted in Greece, which is one of the main tobacco-producing countries. METHODS: A total of 1,020 seasonal and permanent tobacco workers (188 men and 832 women) were studied in a factory in Thessaloniki. The study included: 1) completion of a questionnaire (British Medical Research Council 1986), 2) spirometry and 3) rhinomanometry. At the same time, tobacco dust levels in the working environment were measured. As controls, 469 workers (87 men and 382 women) at a Thessaloniki hospital were used. Seventy six workers with nasal symptoms underwent: 1) special nasal provocation test with tobacco dust antigen, 2) skin prick tests, and 3) measurement of total IgE, specific IgE and specific IgG against tobacco protein. RESULTS: Very high levels of total suspended dust were found in work site air (45.3-54.4 mg/m3). The prevalence of chronic bronchitis was 8.7 % versus 20.6 % in controls. Chronic obstructive pulmonary disease was found in 13 workers (1.3 %) and in 16 controls (3.4 %). FEV1 %pred, FVC %pred and the FEV1/FVC ratio were lower in controls, whereas FEF25-75 % %pred was lower in workers. There were no workers with bronchial asthma or extrinsic allergic alveolitis. Rhinitis was reported by 27.3 % of the workers versus 17.9 % of controls, whereas nasal flows were 563+/-211 versus 645 +/- 321 ml/sec, respectively. According to the results of skin prick tests, six workers were sensitized to dried tobacco leaf dust. CONCLUSIONS: The results of our study do not support an association between the development of chronic diseases of the lower respiratory system and pollutants associated with the processing of dried tobacco leaves. In contrast, an association between disorders of the upper airways and tobacco dust in work sites is postulated.

Respiratory effects in workers processing dried tobacco leaves

Objectives: The aim of this study was to examine the pollution level of the occupational environment and to investigate the effects of occupational exposure to tobacco dust on the respiratory system of tobacco workers. No such study has previously been conducted in Greece, which is one of the main tobacco-producing countries. Methods: A total of 1,020 seasonal and permanent tobacco workers (188 men and 832 women) were studied in a factory in Thessaloniki. The study included: 1) completion of a questionnaire (British Medical Research Council 1986), 2) spirometry and 3) rhinomanometry. At the same time, tobacco dust levels in the working environment were measured. As controls, 469 workers (87 men and 382 women) at a Thessaloniki hospital were used. Seventy six workers with nasal symptoms underwent: 1) special nasal provocation test with tobacco dust antigen, 2) skin prick tests, and 3) measurement of total IgE, specific IgE and specific IgG against tobacco protein. Results: Very high levels of total suspended dust were found in work site air (45.3-54.4 mg/m3). The prevalence of chronic bronchitis was 8.7 % versus 20.6 % in controls. Chronic obstructive pulmonary disease was found in 13 workers (1.3 %) and in 16 controls (3.4 %). FEV1 %pred, FVC %pred and the FEV1/FVC ratio were lower in controls, whereas FEF25-75 % %pred was lower in workers. There were no workers with bronchial asthma or extrinsic allergic alveolitis. Rhinitis was reported by 27.3 % of the workers versus 17.9 % of controls, whereas nasal flows were 563±211 versus 645 ± 321 ml/sec, respectively. According to the results of skin prick tests, six workers were sensitized to dried tobacco leaf dust. Conclusions: The results of our study do not support an association between the development of chronic diseases of the lower respiratory system and pollutants associated with the processing of dried tobacco leaves. In contrast, an association between disorders of the upper airways and tobacco dust in work sites is postulated (AU)

Objetivos: El propósito del estudio era examinar el nivel de contaminación del entorno de trabajo e investigar los efectos de la exposición laboral al polvo de tabaco sobre el aparato respiratorio de los trabajadores de la industria tabacalera. Fue el primer estudio de estas características realizado en Grecia, uno de los principales países productores de tabaco. Métodos: Se estudiaron los casos de 1.020 trabajadores temporales y permanentes de la industria tabacalera (188 hombres y 832 mujeres) en una fábrica de Tesalónica. El estudio consistió en los siguientes pasos: 1) cumplimentar un cuestionario (Consejo Bri- tánico de Investigaciones Médicas, 1986); 2) espirometría, y 3) rinomanometría. Al mismo tiempo, se midieron los niveles de polvo de tabaco en el entorno de trabajo. Se emplearon como controles 469 trabajadores (87 hombres y 382 mujeres) del hospital de Tesalónica. Se sometieron 76 trabajadores con síntomas nasales a los siguientes procedimientos: 1) prueba de provocación nasal especial con polvo de tabaco como antígeno; 2) pruebas cutáneas, y 3) medición de la IgE total, la IgE específica y la IgG específica contra proteína de tabaco. Resultados: En el aire del entorno de trabajo se observaron niveles muy elevados de polvo suspendido total (45,3-54,4 mg/m3). La prevalencia de la bronquitis crónica era del 8,7 por ciento, frente al 20,6 por ciento de los controles. Se observó enfermedad pulmonar obstructiva crónica (EPOC) en 13 trabajadores (1,3 por ciento) y en 16 controles (3,4 por ciento). Los valores del porcentaje predicho de FEV1y FVC, así como el cociente FEV1/FVC resultaron inferiores en los controles, mientras que el porcentaje predicho de FEF25-75 por ciento era inferior en los trabajadores. Ningún trabajador presentaba asma bronquial ni alveolitis alérgica extrínseca. Se observó rinitis en un 27,3 por ciento de los trabajadores frente al 17,9 por ciento de los controles, mientras que los flujos nasales resultaron ser de 563ñ211 frente a 645ñ321 ml/seg, respectivamente. Según las pruebas cutáneas, 6 trabajadores presentaban sensibilidad al polvo de las hojas secas de tabaco. Conclusiones: Los resultados de nuestro estudio no respaldan una relación entre el desarrollo de enfermedades crónicas del tracto respiratorio inferior y los contaminantes asociados a la manipulación de hojas secas de tabaco. En cambio, se postula una asociación entre los trastornos del tracto respiratorio superior y el polvo de tabaco de los entornos de trabajo (AU)

The prevalence of allergic asthma and rhinitis in children of Polichni, Thessaloniki.

AIM: To define the prevalence of asthma and rhinitis in primary school children in the Polichni Municipality of the city of Thessaloniki. METHODS AND RESULTS: The parents of 2005 students living in the area of Polichni completed a questionnaire for the detection of pulmonary disease in childhood. Of 493 children who gave positive answers to the questions about allergies, asthma and rhinitis, 203 were excluded after an interview with the parents, because they suffered from either atopic dermatitis or drug allergy or had normal lgE levels. Of the remaining children, 290 were further examined: methacholine test was positive in 109, exercise test was positive in 67, nasal provocation test with histamine was positive in 244, and rhinodilation test with tramazoline was positive in 206. Skin prick tests were positive in 142 children (90 to grass-cereal pollen, 66 to acarea and 59 to Parietaria officinalis). CONCLUSIONS: We found that 168 children suffered from rhinitis, 84 from both asthma and rhinitis concurrently and 38 from asthma alone. Only 37 % of the parents knew that their children suffered from asthma, while even fewer (32 %) knew that their children had rhinitis. The prevalence of asthma was 6.1 % and that of rhinitis was 12.6 % among children aged 9-12 years in the area of Polichni, Thessaloniki. Childhood rhinitis and asthma seem to be frequently underdiagnosed and undertreated.

The prevalence of allergic asthma and rhinitis in children of Polichni, Thessaloniki

Aim: To define the prevalence of asthma and rhinitis in primary school children in the Polichni Municipality of the city of Thessaloniki. Methods and results: The parents of 2005 students living in the area of Polichni completed a questionnaire for the detection of pulmonary disease in childhood. Of 493 children who gave positive answers to the questions about allergies, asthma and rhinitis, 203 were excluded after an interview with the parents, because they suffered from either atopic dermatitis or drug allergy or had normal lgE levels. Of the remaining children, 290 were further examined: methacholine test was positive in 109, exercise test was positive in 67, nasal provocation test with histamine was positive in 244, and rhinodilation test with tramazoline was positive in 206. Skin prick tests were positive in 142 children (90 to grass-cereal pollen, 66 to acarea and 59 to Parietaria officinalis). Conclusions: We found that 168 children suffered from rhinitis, 84 from both asthma and rhinitis concurrently and 38 from asthma alone. Only 37 % of the parents knew that their children suffered from asthma, while even fewer (32 %) knew that their children had rhinitis. The prevalence of asthma was 6.1 % and that of rhinitis was 12.6 % among children aged 9-12 years in the area of Polichni, Thessaloniki. Childhood rhinitis and asthma seem to be frequently underdiagnosed and undertreated (AU)

Información básica: El objetivo del estudio era definir la prevalencia de asma y rinitis en estudiantes de educación primaria en colegios del municipio de Polichni en la ciudad de Tesalónica. Métodos y resultados: Los padres de 2.005 estudiantes, que vivían en el área de Polichni, rellenaron un cuestionario para la detección de enfermedades pulmonares durante la infancia. De los 493 niños que respondieron de manera positiva a las preguntas referentes a alergias, asma y rinitis, se excluyó a 203 después de una entrevista con los padres porque padecían dermatitis atópica o alergia a fármacos, o presentaban valores normales de IgE. Por lo que respecta a los otros niños, se examinó con más detenimiento a 290; 109 respondieron positivamente a la prueba de la metacolina, 67 realizaron una prueba de esfuerzo positiva, 244 una prueba de provocación nasal positiva con histamina y 206 una prueba positiva de rinodilatación con tramazolina, mientras que las pruebas de punción cutánea fueron positivas en 142 niños (90 a polen de gramíneas-cereales, 66 a ácaros y 59 a Parietaria officinalis). Conclusiones: Se comprobó que 168 niños presentaban rinitis, 84 asma y rinitis al mismo tiempo y 38 sólo asma. Únicamente el 37 por ciento de los padres sabían que sus hijos padecían asma, mientras que un porcentaje aún menor (32 por ciento) sabía que sus hijos tenían rinitis. Se observó que la prevalencia de asma es del 6,1 por ciento, mientras que la de la rinitis es del 12,6 por ciento en los niños de 9-12 años del área de Polichni en Tesalónica. Parece que la rinitis y el asma durante la infancia suelen ser enfermedades diagnosticadas y tratadas insuficientemente (AU)

Tumor necrosis factor-alpha serum levels, weight loss and tissue oxygenation in chronic obstructive pulmonary disease.

Weight loss has been recognized as a feature of advanced emphysema and a factor of poor prognosis, but its mechanisms remain obscure. Studies have demonstrated high serum concentrations of TNF-a (cachexin) in chronic obstructive pulmonary disease (COPD) patients with emphysema. Pink puffers (PP) COPD patients have worse tissue oxygenation when compared with blue bloaters (BB) COPD patients. Consequently, PP patients would become cachectic, whereas BB patients with better tissue oxygenation would not. The aim of this study is to test the hypothesis that malnutrition in emphysema is a cytokine-mediated marker of chronic progressive tissue hypoxia. Thirty male COPD patients, without clinical or laboratory evidence of infection and severe air way obstruction (FEV1 < 1.5 l) were allocated: 16 as pink puffers (PP) and 14 as blue bloaters (BB). Lung function measurements included FEV1, FVC, RV, TLC, DLCO and arterial blood gases on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA). Tissue oxygenation was assessed from oxygen delivery (DO2), PvO2 and oxygen extraction ratio (O2ER) obtained after right heart catheterization with Swan Ganz catheter. PP patients demonstrated lower DLCO and higher TLC, FRC and PaO2 from BB. We found that oxygen delivery was better in our BB than in PP patients (CI 2.9 +/- 0.2 vs 2.5 +/- 0.4 l/min/m2--P < 0.01, DO2 16.1 +/- 2.1 vs 13.1 +/- 0.2 ml/min/kg--P < 0.001) and the same was found for tissue oxygenation (PvO2 34.6 +/- 2.9 vs 31.2 +/- 3.8 mmHg--P < 0.01, O2ER 0.27 +/- 0.02 vs 0.34 +/- 0.06%--P < 0.001). The TNF-a values were higher in PP (31.3 +/- 26 pg/ml vs 15.2 +/- 9.9 pg/ml--P < 0.05) and their percent fat-free mass (%FFM) was 49.6 +/- 11.5 vs 42 +/- 8%--P < 0.001. We found that COPD patients with lower DO2 had increased TNF-a levels; but the correlations between TNF-a serum levels and PvO2 or O2ER were not statistically significant. TNF-a levels were elevated in PP patients with tissue hypoxia and may be a factor contributing to the weight loss of these patients.

Correlation of rCBF (SPECT), CSF tau, and cognitive function in patients with dementia of the Alzheimer's type, other types of dementia, and control subjects.

BACKGROUND: The diagnosis of Alzheimer's disease (AD) during life remains difficult and a definite diagnosis of AD relies on histopathological confirmation at post-mortem or by cerebral biopsy. It is well known that levels of tau proteins are consistently and significantly increased in the cerebrospinal fluid (CSF) of Alzheimer's patients versus levels in normal controls. However, the sole use of this biochemical marker as a test for AD is hampered by mediocre specificity, since tau concentrations may also be elevated in certain other neurological disorders (OND). Studies of the regional cerebral blood flow (rCBF) are widely performed because of their convenience and usefulness in a variety of neurological disorders. Most studies have reported high diagnostic accuracy for brain perfusion single-photon emission tomography (SPECT) in Alzheimer's disease. METHODS: In order to improve specificity, in this study, correlation of 99mTc-HMPAO SPECT scanning and CSF tau protein levels was made in 117 patients with AD, 67 patients with OND (26 of which had other dementias), and 23 age-matched controls. Means and standard deviations of tau protein levels were 297, 42 +/- 221, 12 in AD patients and 78, 07 +/- 98, 51 in patients with OND (p = 0.0006). No correlation was noted between CSF tau protein levels and age, duration of the disease, and neuropsychological scores of mini-mental state examination (MMSE), Cambridge Cognitive Examination (CAMCOG), and Functional Rating Scale for Symptoms of Dementia (FRSSD). FINDINGS: There was a bilateral parietal and temporal hypoperfusion in patients with AD in SPECT in comparison to normal subjects (p < 0.05) and there was a statistical correlation between this hypoperfusion and neuropsychological tests, such as MMSE and CAMCOG (p < 0.01). There was no correlation between tau protein levels and hypoperfusion in SPECT. INTERPRETATION: Conclusively, the correlation between elevated levels of tau proteins and hypoperfusion in SPECT in AD patients therefore cannot improve the specificity of tests in AD and this means that the determination of CSF tau proteins levels is not a specific diagnostic test for AD.

Superoxide dismutase activity in early and advanced Parkinson's disease.

Superoxide dismutase (SOD) is an enzyme system that is implicated in the oxidant stress model of Parkinson's disease (PD) pathogenesis. This study was designed to assess SOD activity in whole blood and red blood cells of PD patients in early and advanced stages of the disease. Fifteen PD patients in stage I and II (group A) and 15 in stage III and IV (group B) as well as 15 normal controls were included in the study. SOD activity was assessed in whole blood and red blood cells. Group B patients showed a statistically significant decrease of SOD activity in whole blood and in red blood cells. A negative correlation between SOD activity and duration of the disease was observed, while there was no relationship between L-Dopa treatment and SOD activity. Our results indicate that a defect in SOD activity develops over time in PD. Whether this is a later manifestation of antioxidant mechanism deterioration or simply an epiphenomenon remains unclear.

Clinical evaluation of four different high-flux hemodialyzers under conventional conditions in vivo.

Four types of high-flux hemodialyzers, Primus 2000 (high-flux polysulfone 2.0 m2), Altra-Flux 170 G (cellulose diacetate 1.7 m2), FLX-15 GW (polyester-polymer alloy 1.5 m2) and PAN-85 DX (polyacrylonitrile 1.7 m2) were evaluated in vivo. A total of 12 stable chronic hemodialysis patients participated in the study and each type of dialyzer was tested once in 9 of them. Blood samples for the measurement of BUN, creatinine, phosphate, uric acid, albumin and beta2-microglobulin (beta2M) were drawn before and 5 min after the end of the study dialysis. During dialysis, which was performed in all patients with a blood flow rate of 250 ml/min for 240 min, the dialysate (550-600 ml/min) was collected every hour and samples were drawn for the measurements of all the above substances. The mean total amount of low-molecular substances removed per session by each dialyzer was very close to 19.5 g for urea, 2.0 g for creatinine, 0.9 g for phosphate and 1 g for uric acid. The one-third (30-33%) of the above amounts were removed during the first hour of dialysis. Dialyzers' clearances for creatinine and uric acid were significantly higher in Primus dialyzer comparing to FLX-15 GW (p < 0.05) while the clearance for urea showed a borderline significance (p = 0.055). No difference was found either among Altra-Flux 170 G, FLX-15 GW and PAN-85 DX or between Primus and PAN-85 DX dialyzers. Phosphate clearance did not show any difference among the four dialyzers. The lowest amount of albumin removed per session was 0.75 g by PAN-85 DX and the highest 1.8 g by FLX-15 GW, while the equivalents for beta2M were 80 mg by Altra-Flux 170 G and 142 mg by PAN-85 DX. A significant adsorption of beta2M on these dialysis membranes was indicated by the combination of a satisfactory serum beta2M reduction ratio (post-/predialysis values = 0.52, 0.77, 0.60, 0.55) with a reduced beta2M clearance (23.9, 13.6, 20.2, 25.1 ml/min). During the first hour of dialysis, in comparison to the following time, the highest amounts of albumin and beta2M (expressed as percentage of total) were removed by the Primus 2000 dialyzer. Our results indicate that under conventional conditions small differences in the surface area of the high-flux dialyzers are unimportant regarding the removal of low molecules. However, the composition of the membrane seems to play an important role in the removal of high-molecular substances.

Comparative efficacy of salbutamol and salmeterol in exercise-induced asthma.

This study compared the protection provided by salbutamol and salmeterol against exercise-induced asthma. Asthmatic patients (n = 12) with exercise-induced asthma were exercised submaximally for 6 min on a treadmill 1, 6 and 12 h after inhalation of 200 micrograms salbutamol or 50 micrograms salmeterol. Each patient also took baseline exercise 1 h after two puffs of placebo. Two days later the drugs were administered in a double-blind trial of crossover design with an interval of 48 h between the two treatments. The main parameters measured were: air flow with a Wright flowmeter and mediator concentrations (histamine, leucotriene and prostaglandin D2 measured by radioimmunoassay) in venous blood, which was withdrawn before and 4 min after each exercise period. The maximum percentage bronchoconstriction recorded following placebo was 29 +/- 4% and following salbutamol inhalation it was 4 +/- 4%, 20 +/- 13%, 27 +/- 10%, respectively, for the exercise periods performed 1, 6 and 12 h after inhalation of the drug. Following salmeterol, the corresponding figures were 3 +/- 4%, 3 +/- 3% and 11 +/- 9%. The concentrations of mediator in plasma were significantly increased after exercise. Salbutamol and salmeterol intake reduced these concentrations both when the patients were at rest and following the exercise period. This effect of both drugs on the mediators corresponded with the protection they provided against exercise-induced asthma and was maintained for 12 h after salmeterol inhalation and for 6 h after salbutamol inhalation.

A simple staining method for vaginal smears using red ink.

In adult rhesus monkeys each phase of 37 menstrual cycles was accurately classified by cellular identification of vaginal smears stained with red ink. This technic was simple, quick, and inexpensive, and produced well-stained slides in a few seconds.

Fallopian tube occlusion in rabbits with silicone rubber.

A new system for transcervically blocking the Fallopian tubes with cured-in-place silicone rubber has great potential for fertility control. Good retention, antifertility efficacy, and retrievability were observed in rabbits, and no adverse tissue reactions were seen in oviducts containing silicone elastomer. Continuing studies with rabbits and rhesus monkeys attempt to determine long term efficacy and histologic changes.

The antifertility effect and improved tolerance of copper bearing hydrogel coated intrauterine devices in rabbits.

PIP: Polyethylene IUDs covered with hydrogel over copper wire were tested in 20 New Zealand white rabbits. None of the rabbits with copper-bearing hydrogel-coated IUDs became pregnant as compared with 86.6% of the sham-operated controls and 38.5% of those with only hydrogel-coated IUDs. 50% of the hydrogel-coated IUDs with copper were expelled; no fragmentation of either copper or hydrogel was seen. The total white blood cell count in uterine fluid was increased 68.1% by copper-bearing hydrogel-coated IUDs. It is concluded that hydrogel coating of copper IUDs enhances tolerance of the devices, improves the contraception, and reduces the expulsion rate. Copper diffusion from the hydrogel-coated IUD was 37.5 mcg/ml.^ieng