Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Satisfaction,quality of life and therapy adherence assessment in real life patients transitioning from vitamin K antagonists to direct oral anticoagulants

Journal of Thrombosis and Thrombolysis - Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed...     

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

PurposeTo investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene.MethodsThis longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency.ResultsFrom an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of −0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles.ConclusionsWe described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.     

Diminished Retention of Food in the Proximal Stomach Correlates with Increased Acidic Reflux in Patients with Gastroesophageal Reflux Disease and Dyspeptic Symptoms

This work aimed at evaluating the intragastric distribution of food in patients with GERD and dyspepsia and its relationship to acidic reflux episodes. Gastric emptying and food retention in the proximal stomach were evaluated by scintigraphy in 12 healthy subjects and 19 patients with GERD and dyspepsia after a liquid test meal. Patients also underwent 24-hr esophageal pH monitoring, which included a 2-hr postprandial period following a similar test meal. Total gastric emptying was similar in patients and controls, whereas proximal gastric retention (AUCprox/AUCtot) was significantly decreased in patients (mean +/- SD: 0.48 +/- 0.07 vs. 0.56 +/- 0.06; P = 0.02). Within the GERD-dyspepsia group, a significant negative correlation was found between proximal gastric retention and the number of acidic reflux episodes. We concluded that abnormally decreased retention of gastric contents in the proximal stomach after a liquid meal may contribute to the pathogenesis of acidic reflux episodes in patients with GERD and dyspepsia.     

Absence of IFNγ expression induces neuronal degeneration in the spinal cord of adult mice

Background  

Interferon gamma (IFNγ) is a pro-inflammatory cytokine, which may be up-regulated after trauma to the peripheral or central nervous system. Such changes include reactive gliosis and synaptic plasticity that are considered important responses to the proper regenerative response after injury. Also, IFNγ is involved in the upregulation of the major histocompatibility complex class I (MHC class I), which has recently been shown to play an important role in the synaptic plasticity process following axotomy. There is also evidence that IFNγ may interfere in the differentiation and survival of neuronal cells. However, little is known about the effects of IFNγ absence on spinal cord neurons after injury.     

Gastroesophageal reflux disease and postlaryngectomy tracheoesophageal fistula

The objective of this study is to evaluate the incidence of pathologic gastroesophageal reflux in laryngectomized patient with phonatory prosthesis, analyzing potential related problems and appraising, at the same time, the effectiveness of a therapeutic protocol. A retrospective study was conducted on 43 phonatory prosthesis patients who had problems with regard to recurrent tracheoesophageal granulations, the need of frequent prosthesis replacement, within a 3-month period, and unsatisfactory vocal results. Such patients underwent physical examination of the fistula region and of the neopharynx and were submitted to esophagogastroduodenoscopy. Moreover the group of patients underwent a therapeutic protocol and were re-evaluated posttreatment, examining fistula region both on the tracheal side and on the esophageal side through videolaryngostroboscopy. Of the 43 recruited patients 13 (30%) presented tracheoesophageal granulations, 20 (46.5%) unsatisfactory vocal results and 10 (23.5%) frequent prosthesis replacement, within a 3-month period, due to abnormal biofilm development. In particular, of the 13 patients who had recurrent granulations, the evaluation results revealed the presence of gastroesophageal reflux disease (GERD) in 6 cases (46%). In the group of patients presenting unsatisfactory vocal results GERD was shown in 13 cases (65%). In the third group of patients GERD was found in two cases (20%). The overall analysis of the data gathered, allowed to identify GERD in 21 (49%) of the 43 patients submitted to the study. The results posttreatment indicated, in the first group, the disappearance or a significant (>75%) volume reduction of such formation in five cases (38%, p = 0.002). In the second group an overall improvement in the quality of voice was displayed at least for 12 patients (60%, p = 0.0001). Finally in the last group an increase of the prosthesis life was recorded in four (40%, p = 0.05) of the ten patients who had the need of prosthesis replacement within 3 months. Also the 22 GERD negative cases (51%) underwent the treatment, therefore representing the control group, whose posttreatment results showed substantial modifications in just two cases (9%). The data obtained suggest a high degree of correlation between the presence of pathologic gastric reflux and the partial or total prosthesis failure. The introduction of a specific therapeutic protocol has allowed to improve the quality of prosthesis (QoP) in 22 of the 43 patients (p < 0.001) who had a pathologic condition of the fistula and of the prosthesis.     

TDI技术评价卡维地洛对高血压患者左室舒张功能的影响

目的:应用组织多普勒显像(TDI)技术评价卡维地洛对高血压患者左室舒张功能的影响.方法:对30例高血压给予卡维地洛治疗24周.治疗前、治疗后12周、24周用TDI技术测量左室收缩期二尖瓣环平均舒张早期运动速度(Ea)、舒张晚期运动速度(Aa)及Ea/Aa,并与血流多普勒指标E波速度(E)、A波速度(A)、E/A进行比较,观察降压效果及对左室舒张功能的影响.结果:卡维地洛治疗12周后收缩压(SBP)、舒张压(DBP)、心率(HR)均较治疗前下降(P＜0.05),Ea、Ea/Aa均较治疗前升高(P＜0.05),治疗24周后E、E/A较治疗前升高(P＜0.05),Aa较治疗前降低(P＜0.05),Ea、Ea/Aa有进一步改善的趋势(P＜0.05).结论:TDI技术在评价左室舒张功能方面较二尖瓣血流频谱更敏感;卡维地洛对轻、中度高血压具有良好的降压作用,且能改善患者左室舒张功能.