Differences in molecular sensitization profiles between a Spanish and Latin American mite allergic patients.

BACKGROUND AND OBJECTIVE: To analyze the sensitization pattern to Dermatophagoides pteronyssinus and to associate the diagnostic findings and clinical severity in 218 allergic patients from two different continents. METHODS: Mite allergic patients were recruited by the Allergology departments from Latin America (n=88: Colombia, Costa Rica and Guatemala) and Spain (N=130). All patients had allergic rhinitis with or without asthma and positive skin prick test results to D. pteronyssinus. Specific IgE levels to D. pteronyssinus, D. farinae, Der p 1, Der p 2, and Der p 23 were quantified by ImmunoCAP system (ThermoFisher Scientific). Allergenic profile was also determined by western blot. Comparative Statistical analysis was performed by GraphPad software. RESULTS: Patients recognized most frequently Der p 2 (79%) followed by Der p 1 (73%), and Der p 23 (69%) allergens. The percentage of asthmatic patients increases with the number of sensitizations however none statistically significant differences were found. Interestingly, asthmatic patients presented the highest median levels of total IgE and specific IgE levels of D. pteronyssinus and molecular allergens, mainly Der p 2. Analysing the two different populations, Spanish patients were predominantly sensitized to Der p 2 (88.46%) and Der p 1 (83.84%), whereas Latin American population were more sensitized to Der p 23. CONCLUSION: Our data support the relevance of Der p 2 in mite allergy as the major allergen, with the high number of patients sensitized to it and its importance in the development of asthma. Sensitization to Der p 23 was more important in Latin America.

Initial experience with thulium fiber laser for prostate enucleation: Analysis of the intraoperative and short-term outcomes in a prospective, multicenter cohort.

INTRODUCTION: Holmium laser enucleation of the prostate has rapidly become the gold standard for the surgical treatment of benign prostate hyperplasia, although thulium fiber laser (TFL) has also been postulated as an effective and safe alternative for prostate enucleation. The aim of this study is to describe our initial experience with the TFL for endoscopic enucleation of the prostate. MATERIAL AND METHODS: All patients proposed to TFL prostate enucleation were included in the analysis, regardless their prostate volume, catheter status and severity of symptoms, in 3 centers. Preoperative characteristics, intraoperative times and functional 3-months follow-up variables were collected, along with complications. RESULTS: Fifty-six patients were available, with a mean age of 68.7 years. Enucleation and morcellation efficiencies were 2.04 and 7.47 g/min, respectively. Median hospital stay was one day. Comparable functional data, pre and 3-month post-surgery was: mean prostate volume 88.9 vs 21.3 g, maximum urinary flow 13.2 vs 27.3 ml/s, post-void residual volume 149 vs 7.8 ml, prostatic specific antigen level 11.2 vs 1 ng/ml, and International Prostate Symptom Score 20.75 vs 3.96. Fourteen out of 56 (25%) patients presented with complications grade ≤2, according to the Clavien-Dindo classification. DISCUSSION: With wider evidence for other urological indications, very recent evidence about the suitability of TFL for prostate enucleation has arisen, since the first case described in 2021. Our results seem to back up these previous successful experiences as long as we obtained good intraoperative and short term follow-up functional results. However, there is still a need of longer follow-up data. CONCLUSIONS: TFL represents a novel technology for prostate enucleation, with a good intraoperative and short follow-up functional results, and a safety profile similar to the observed for those techniques that have been wider used for this indication. Further studies with longer follow-up periods and comparative with these other techniques are necessary.

Differential gene-expression analysis defines a molecular pattern related to olive pollen allergy.

Analysis of gene-expression profiles by microarrays is useful for characterization of candidate genes, key regulatory networks, and to define phenotypes or molecular signatures which improve the diagnosis and/or classification of the allergic processes. We have used this approach in the study of olive pollen response in order to find differential molecular markers among responders and non-responders to this allergenic source. Five clinical groups, non-allergic, asymptomatic, allergic but not to olive pollen, untreated-olive-pollen allergic patients and olive-pollen allergic patients (under specific-immunotherapy), were assessed during and outside pollen seasons. Whole-genome gene expression analysis was performed in RNAs extracted from PBMCs. After assessment of data quality and principal components analysis (PCA), differential gene-expression, by multiple testing and, functional analyses by KEGG, for pathways and Gene-Ontology for biological processes were performed. Relevance was defined by fold change and corrected P values (less than 0.05). The most differential genes were validated by qRT-PCR in a larger set of individuals. Interestingly, gene-expression profiling obtained by PCA clearly showed five clusters of samples that correlated with the five clinical groups. Furthermore, differential gene expression and functional analyses revealed differential genes and pathways in the five clinical groups. The 93 most significant genes found were validated, and one set of 35 genes was able to discriminate profiles of olive pollen response. Our results, in addition to providing new information on allergic response, define a possible molecular signature for olive pollen allergy which could be useful for the diagnosis and treatment of this and other sensitizations.

Growth, allergen profile and microbiome studies in Dermatophagoides pteronyssinus cultures.

Mites are mass-cultured to manufacture allergen extracts for allergy diagnostics and therapeutic treatment. This study focused on characterizing the growth, the allergen profile, and the microbiome of Dermatophagoides pteronyssinus cultures. Mite population, protein profile, total protein content and major allergen levels (Der p 1, Der p 2, Der p 23) were monitored at different times of three independent cultures. The allergenicity was studied by immunoblot using a pool of sera from allergic patients. Mite microbiome was characterized by sequencing the 16S rRNA gene from 600 adult mites from the last day of the culture. Endotoxin content was also analyzed. The cultures had a fast and unrelenting evolution. Mite density, total protein content, major allergen levels and the allergenicity were increased progressively during the cultures. Regarding the microbiome studies, the results confirm the presence of non-pathogenic bacteria, being firmicutes and actinobacteria the most common bacterial taxa, with a very low content of Gram-negative bacteria and endotoxin content. The allergenicity and levels of the main allergens in the mite cultures are objective methods useful to monitor the mite culture that help to produce standardized allergen extracts. The high presence of Gram-positive bacteria found limits the possibility for vaccine contamination by bacterial endotoxins.

Immunological mechanisms involved in the human response to a dog dander allergoid.

BACKGROUND: Dog allergens are a common cause of allergic sensitisation and trigger respiratory symptoms worldwide. However, clinical evidence regarding dog immunotherapy is limited. Therefore, the aim of this study was to analyse the immunomodulatory properties of a new allergoid from dog dander, thereby deepening the understanding of the molecular mechanisms involved in the reestablishment of the tolerogenic response. METHODS: Three independent batches of dog dander native and allergoid allergen extracts were manufactured and characterised. Allergenic profiles were analysed by the identification of all dog allergens and quantification of the major allergens Can f 1 and Can f 5. The allergenicity profile of the allergoid was studied using biological potency and basophil activation tests. In vitro immunomodulatory parameters was evaluated as the capacity of the allergoid to induce IgG antibodies that block IgE binding to the allergen and cytokine promotion (IFN-γ, IL-4, IL-6, IL-10, IL-13, and TNF-α) in PBMCs from allergic donors. RESULTS: The presence of all dog allergens, including Can f 1 and Can f 5, was confirmed in both types of extracts. The new allergoid showed a low IgE binding capacity, which significantly affected the activation of effector cells, such as basophils. The IgG antibodies induced by the allergoid in rabbits blocked human IgE binding epitopes on the dog native extract and induced Th1 and Treg responses by increasing IFN-γ and IL-10 levels in PBMCs from allergic donors. CONCLUSION: This new dog dander allergoid containing Can f 1 and Can f 5 showed a low capacity to bind IgE and to activate basophils in dog allergic patients. Furthermore, it showed potent activation of Th1 mediators and induction of tolerance through Treg activation. This allergoid could offer a safer profile than the native extract and could be an effective immunotherapy treatment for dog allergic patients.

Immunological Mechanisms in Allergic Diseases and Allergen Tolerance: The Role of Treg Cells.

The immune system regulates itself to establish an appropriate immune response to potentially harmful pathogens while tolerating harmless environmental antigens and self-antigens. A central role in this balance is played by regulatory T cells (Tregs) through various ways of actions. By means of molecule secretion and cell-cell contact mechanisms, Tregs may have the capacity to modulate effector T cells and suppress the action of proinflammatory cytokines across a broad range of cell types. As a result, abnormal regulatory T cell function has been pointed as a main cause in the development of allergic diseases, a major public health problem in industrialized countries, with a high socioeconomic impact. This prevalence and impact have created an international interest in improving the allergy diagnosis and therapy. Additionally, research has sought to gain a better understanding of the molecular mechanisms underlining this kind of disease, in order to a better management. At this respect, the role of Treg cells is one of the most promising areas of research, mainly because of their potential use as new immunotherapeutical approaches. Therefore, the aim of this review is to update the existing knowledge of the role of Tregs in this pathology deepening in their implication in allergen-specific therapy (AIT).

Heterogeneity of allergen content in male dog urine and dander

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[Pericardial defect with atrial herniation]. / Defecto pericárdico con herniación auricular.

Pericardial defects are rare in childhood and outcome is usually benign. Patients can be asymptomatic, but they may experience vague chest pain, angina, myocardial ischemia, emboli, and arrhythmia and some cases of sudden death have even been described in the literature. We report the case of a 3-month-old girl who, in the context of an episode of fever, underwent chest X-ray examination, which showed a left heart border anomaly. This finding strongly suggested a congenital partial pericardial defect, which was subsequently confirmed by other techniques. The interest of this case lies in the ability of the pediatrician to establish a presumptive diagnosis by examining the chest X-ray. We conclude by stressing the need for a high degree suspicion for congenital heart anomalies because of the life-threatening nature of some partial pericardial defects, which can lead to left-ventricular herniation.

[Cardiovascular changes in a group of patients with heredoataxia. Clinical, electrocardiographic and echocardiographic findings]. / Alteraciones cardiovasculares en un grupo de pacientes con heredoataxia. Hallazgos clínicos, electro y ecocardiográficos.

INTRODUCTION: Heredoataxias form a group of degenerative diseases of the nervous system, which are progressive and hand sound in particular families. MATERIAL AND METHODS: Between August 1994 and September 1995. 14 patients diagnosed as having heredoataxia were studied after admission to our hospital. Eight of these had Friedrich's ataxia (group A) and 6 had other types of ataxia (group B). A standard set of investigations were done, including clinical examination, laboratory tests (such as glycaemia and a lipidogram) to evaluate coronary risk factors. A 12 lead electrocardiogram and bidimensional and m mode echocardiogram were also done to detect disorders of conduction, changes in morphology and cardiac function, together with functional cardiovascular and neurological scales. The patients studied were between 14 and 41 years of age. RESULTS: The most frequent cardiovascular symptom was dyspnoea of effort. Changes on the electrocardiogram were seen in 92% of the patients, mainly from Group A (100%) and were due to alterations of ventricular repolarization and non-specific alterations of conduction and of rhythm. Echocardiogram changes were found in 42.8% of the patients, most frequently due to an increase in the myocardial mass of the left ventricle. CONCLUSIONS: Close correlation between age of onset and duration of the illness, and functional cardiovascular impairment was only seen in patients of Group A, in whom there was an earlier onset of the condition.

Percutaneous mechanical mitral commissurotomy performed with a Cribier's metallic valvulotome. Initial results.

OBJECTIVE: To evaluate the immediate results of percutaneous mechanical mitral commissurotomy. METHODS: Thirty patients underwent percutaneous mechanical mitral commissurotomy performed with a Cribier's metallic valvulotome from 8/11/99 to 2/4/00. Mean age was 30.7 years, and 73.3% were women. With regards to functional class, 63.3% were class III, and 36.7% were class IV. The echocardiographic score had a mean value of 7.5+/- 1.8. RESULTS: The mitral valve area increased from 0.97+/-0.15cm2 to 2.16+/-0.50cm2 (p>0.0001). The mean diastolic gradient decreased from 17.9+/-5.0mmHg to 3.2+/-1.4mmHg. The mean left atrial pressure decreased from 23.6+/-5.4mmHg to 8.6+/-3.1mmHg, (p>0.0001). Systolic pressure in the pulmonary artery decreased from 52.7+/-18.3mmHg to 32.2+/-7.4mmHg. Twenty-nine cases were successful. One patient developed severe mitral regurgitation. Interatrial septal defect was observed and one patient. One patient had cardiac tamponade due to left ventricular perforation. No deaths occurred. CONCLUSION: This method has proven to be safe and efficient in the treatment of rheumatic mitral stenosis. The potential advantage is that it can be used multiple times after sterilization, which decreases procedural costs significantly.

[Fetal bradycardia: a retrospective study in 9 Spanish centers]. / Bradicardia fetal: estudio multicéntrico retrospectivo en 9 hospitales españoles.

OBJECTIVE: The aim of this study is to review the current management and outcomes of fetal bradycardia in 9 Spanish centers. METHODS: Retrospective multicenter study: analysis of all fetuses with bradycardia diagnosed between January 2008 and September 2010. Underlying mechanisms of fetal bradyarrhythmias were studied with echocardiography. RESULTS: A total of 37 cases were registered: 3 sinus bradycardia, 15 blocked atrial bigeminy, and 19 high grade atrioventricular blocks. Sinus bradycardia: 3 cases (100%) were associated with serious diseases. Blocked atrial bigeminy had an excellent outcome, except for one case with post-natal tachyarrhythmia. Of the atrioventricular blocks, 16% were related to congenital heart defects with isomerism, 63% related to the presence of maternal SSA/Ro antibodies, and 21% had unclear etiology. Overall mortality was 20% (37%, if terminations of pregnancy are taken into account). Risk factors for mortality were congenital heart disease, hydrops and/or ventricular dysfunction. Management strategies differed among centers. Steroids were administrated in 73% of immune-mediated atrioventricular blocks, including the only immune-mediated IInd grade block. More than half (58%) of atrioventricular blocks had a pacemaker implanted in a follow-up of 18 months. CONCLUSIONS: Sustained fetal bradycardia requires a comprehensive study in all cases, including those with sinus bradycardia. Blocked atrial bigeminy has a good prognosis, but tachyarrhythmias may develop. Heart block has significant mortality and morbidity rates, and its management is still highly controversial.

Epigenetic regulation analyses of FOXP3 in olive pollen allergy

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Taquicardia fetal: estudio multicéntrico retrospectivo en 9 hospitales españoles / Fetal tachycardia: a retrospective study in 9 Spanish centers

Introducción y objetivo: El tratamiento óptimo de la taquicardia fetal es todavía objeto de controversia. El objetivo de este estudio es revisar el manejo y la evolución de los fetos diagnosticados de taquicardia en 9 centros españoles. Método: Se llevó a cabo un estudio multicéntrico retrospectivo, con análisis de todos los fetos con taquicardia diagnosticados en 9 centros españoles entre enero de 2008 y septiembre de 2010. Resultados: Se registraron 37 casos, un 30% hidrópicos. Un total de 26 casos no presentaba hidropesía; 4 de ellos se diagnosticaron de flutter auricular –cardioversión con éxito en todos, intraútero o posnatalmente– y 22 de taquicardia supraventricular (TSV), 17 con intervalo ventriculoauricular (VA) corto y 5 con intervalo VA largo. El fármaco inicial en la mayoría de los casos fue la digoxina. La taquicardia se controló prenatalmente en el 93% de las TSV con VA corto y en el 50% con VA largo. La digoxina resultó eficaz en los fetos con VA corto, pero ineficaz en los casos con VA largo (p= 0,019). Un feto con TSV con disfunción ventricular falleció. Asociaron hidropesía 11 casos, todos ellos diagnosticados de TSV. La estrategia terapéutica fue muy variable en este grupo. Fallecieron 5 de los fetos hidrópicos: 1 posnatalmente, 2 intraútero muy precozmente tras empezar el tratamiento, y 2 intraútero a pesar de haber convertido a ritmo sinusal con éxito (1 estando en tratamiento con flecainida y 1 con sotalol) . Conclusiones: En nuestra serie se ha registrado una mortalidad muy alta de los fetos hidrópicos. Proponemos un nuevo protocolo de tratamiento concordado para mejorar la evolución de la taquicardia fetal (AU)

Introduction and objective: Optimal treatment for fetal tachycardia is still controversial. The aim of this study is to review the actual management and outcome of fetal tachycardia in 9 Spanish centers. Method: Retrospective multicentric study: analysis of all fetuses with tachycardia diagnosed at 9 Spanish centers between January 2008 and September 2010. Results: 37 cases were registered, 30% of which were hydropic. We had 26 no hydropic cases, of which 4 atrial flutter –all of them successfully cardioverted intrautero or after delivery– and 22 with supraventricular tachycardia (SVT), of which 17 short ventriculo-auricular (VA) interval and 5 long VA interval. Digoxin was the drug of choice in most cases. Prenatal control of the tachycardia was achieved in 93% of treated SVT with short VA interval and 50% of long VA, being digoxine effective in short VA but not long VA interval (p= 0.019). 1 fetus with supraventricular tachycardia with ventricular dysfunction died. 11 cases were hydropic, all of them diagnosed as SVT. Management strategies were highly diverse in this group. 5 patients died: 1 after delivery, 2 intrautero very shortly after starting treatment, and 2 intrautero in spite of being successfully cardioverted to sinus rhythm (1 with sotalol, 1 with flecainide). Conclusions: Hydropic fetuses have shown a high mortality rate in our population, which calls for further studies and unification of criteria. Here we propose a common protocol aimed at improving the outcome of fetal tachycardia (AU)

Bradicardia fetal: estudio multicéntrico retrospectivo en 9 hospitales españoles / Fetal bradycardia: A retrospective study in 9 Spanish centers

OBJETIVO: Revisar el manejo actual y la evolución de la bradicardia fetal en 9 centros españoles. MÉTODO: Estudio multicéntrico retrospectivo: análisis de todos los fetos con bradicardia diagnosticados en 9 centros españoles entre enero de 2008 y septiembre de 2010. Los mecanismos electrofisiológicos responsables de la bradicardia fetal se estudiaron mediante ecocardiografía. RESULTADOS: Se registraron 37 casos: 3 fetos con bradicardia sinusal, 15 con extrasistolia auricular no conducida y 19 con bloqueo auriculoventricular (AV) de alto grado. Bradicardia sinusal: el 100% asoció patologías severas. Extrasistolia auricular no conducida: excelente pronóstico, pero un caso desarrolló posnatalmente taquicardia supraventricular. Entre los bloqueos AV de alto grado, el 16% asociaban cardiopatía congénita con isomerismo, el 63% anticuerpos antiRo/SSA maternos y el 21% fueron de etiología desconocida. La mortalidad global de los bloqueos AV fue del 20% (37% si consideramos la interrupción voluntaria del embarazo). Factores de riesgo fueron: asociar una cardiopatía congénita, hídrops y/o disfunción ventricular. El tratamiento fue variable según el centro, se administraron corticoides en el 73% de los bloqueos de grado III inmunomediados y en el único caso de bloqueo de grado II inmunomediado. En un seguimiento medio de 18 meses, se implantaron marcapasos en el 58% de los bloqueo AV de alto grado. CONCLUSIONES: La bradicardia fetal sostenida precisa siempre de un estudio exhaustivo, incluso en el caso de la bradicardia sinusal. La extrasistolia auricular no conducida tiene buen pronóstico pero puede asociar taquicardia. El bloqueo AV de alto grado fetal tiene todavía una morbimortalidad significativa y su tratamiento es controvertido

OBJECTIVE: The aim of this study is to review the current management and outcomes of fetal bradycardia in 9 Spanish centers. METHODS: Retrospective multicenter study: analysis of all fetuses with bradycardia diagnosed between January 2008 and September 2010. Underlying mechanisms of fetal bradyarrhythmias were studied with echocardiography. RESULTS: A total of 37 cases were registered: 3 sinus bradycardia, 15 blocked atrial bigeminy, and 19 high grade atrioventricular blocks. Sinus bradycardia: 3 cases (100%) were associated with serious diseases. Blocked atrial bigeminy had an excellent outcome, except for one case with post-natal tachyarrhythmia. Of the atrioventricular blocks, 16% were related to congenital heart defects with isomerism, 63% related to the presence of maternal SSA/Ro antibodies, and 21% had unclear etiology. Overall mortality was 20% (37%, if terminations of pregnancy are taken into account). Risk factors for mortality were congenital heart disease, hydrops and/or ventricular dysfunction. Management strategies differed among centers. Steroids were administrated in 73% of immune-mediated atrioventricular blocks, including the only immune-mediated IInd grade block. More than half (58%) of atrioventricular blocks had a pacemaker implanted in a follow-up of 18 months. CONCLUSIONS: Sustained fetal bradycardia requires a comprehensive study in all cases, including those with sinus bradycardia. Blocked atrial bigeminy has a good prognosis, but tachyarrhythmias may develop. Heart block has significant mortality and morbidity rates, and its management is still highly controversial

The effect of chronic phenytoin treatment on serum lipid profile in adult epileptic patients.

Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein cholesterol, apolipoproteins A, A1, and B and gamma-glutamyltransferase (ggt) serum concentrations were measured in 100 adult epileptic patients receiving chronic phenytoin (PHT) treatment and in 100 control subjects. In relation to controls, patients showed higher HDL cholesterol, apolipoproteins A and A1, and ggt levels and lower LDL cholesterol and apolipoprotein B values; the significance of the results was greater in women than in men. Among patients, ggt levels were positively correlated with PHT plasma concentrations; likewise, a negative correlation was found between the apolipoprotein A/A1 ratio and the PHT and ggt plasma levels, and a positive correlation between the apolipoprotein A/A1 ratio and the LDL/HDL cholesterol ratio. These data indicate that PHT exerts a beneficial effect on the serum lipids profile.