Exploratory screening for Fabry’s disease in young adults with cerebrovascular disorders in northern Sardinia

Abstract

Background

The etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabry's disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia.

Methods

For this study, we enrolled 178 patients consecutively admitted to our Neurological Ward for ischemic stroke, transient ischemic attack, intracerebral haemorrhage, neuroradiological evidence of silent infarcts, or white matter lesions possibly related to cerebral vasculopathy at brain MRI, and cerebral venous thrombosis. The qualifying events have to occur between 18 and 55 years of age.

Results

We identified two patients with an α-galactosidase A gene variant, with a prevalence of 0.9 %. According to recent diagnostic criteria, one patient, included for the occurrence of multiple white matter lesions at brain MRI, had a diagnosis of definite FD, the other, included for ischemic stroke, had a diagnosis of uncertain FD.

Conclusions

Our study places in a middle position among studies that found a prevalence of FD up to 4 % and others that did not find any FD patients. Our findings confirm that FD should be considered in the differential diagnosis of patients with juvenile stroke, particularly those with a personal or familial history positive for cerebrovascular events, or evidence of combined cardiologic and/or renal impairment. All types of cerebrovascular disorders should be screened for FD, including patients with white matter lesions possibly related to cerebral vasculopathy at brain MRI.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SVgAe8
via IFTTT

The role of IgE recognition in allergic reactions to Amoxicillin and Clavulanic acid

Abstract

Betalactam (BL) antibiotics are the drugs most frequently involved in IgE-mediated reactions. The culprit BL varies according to consumption patterns, with amoxicillin (AX) more prevalent in Southern Europe and penicillin V in Scandinavian countries.

Nowadays, the combination of AX and clavulanic acid (CLV), is the most highly consumed BL containing medicine worldwide. Both BLs, AX and CLV, can independently be involved in reactions, which poses a diagnostic challenge.

In patients with immediate allergic reactions to AX, two patterns of responses have been described, those responding to benzylpenicillin (cross-reactors) and those selective to AX. In addition, selective reactions to CLV account for around 30% of allergic reactions to the combination AX-CLV. These patterns of IgE recognition could be related to differences in the haptenation process, in the immunological response, or in the BL involved in the first sensitization. In this regard, patients with selective responses to CLV are generally younger than those allergic to AX or benzylpenicillin. So far, no evidence of cross reactivity between CLV and other BLs has been reported. This shows the importance of an accurate diagnosis of CLV allergy, since patients with selective reactions to CLV could take other BLs including AX. Diagnosis can be performed in vivo and in vitro, although no immunoassay currently exists. Research regarding the CLV antigenic determinants and protein conjugates is essential to improve diagnosis.

BLs need to covalently bind to a carrier protein to be immunogenic. The antigenic determinant of AX is the amoxicilloyl amide, but CLV leads to unstable structures, many of which are unknown. Moreover, the nature of the BL-protein conjugates plays an important role in IgE recognition. This review aims to summarise current knowledge on the immunochemistry, diagnostic approaches as well as chemical and proteomic studies for both AX and CLV.

This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Map8s6
via IFTTT

The response to nasal allergen provocation with grass pollen is reduced in patients with chronic rhinosinusitis with nasal polyposis and grass sensitization

Abstract

Background

The majority of grass pollen sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test (NAPT). Chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens.

Objective

We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen sensitized CRSwNP patients.

Methods

Twelve grass pollen sensitized CRSwNP patients underwent NAPT with grass pollen and were compared to 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSwNP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen specific IgE and tryptase were measured in serum and nasal secretions.

Results

NAPT was positive in 6 out of 12 of the grass pollen sensitized CRSwNP patients and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSwNP group two of the patients developed a positive provocation test.

Conclusion And Clinical Relevance

These results show that allergen exposure induces an attenuated clinical response in patients with CRSwNP and sensitization to grass pollen as compared to grass pollen allergic rhinitis patients.

This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Map6Au
via IFTTT

Relationship between Sputum Clusterin Levels and Childhood Asthma

Abstract

Background

Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated.

Objectives

1) To evaluate sputum clusterin levels in children with asthma compared to a control group. 2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness.

Methods

This study included 170 children aged 5–18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay.

Results

Children with stable asthma had a higher clusterin level than healthy controls (4540 [3872–5651] pg/mL vs. 3857 [1054–4369] pg/mL, P < 0.001). The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma (5094 [4243–6257] pg/mL vs. 4110 [1871–4839] pg/mL, P = 0.0017). Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma (1838 [350–4790] pg/mL vs. 4540 [3871–5651] pg/mL, P < 0.001). Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 second (r = − 0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters.

Conclusions and Clinical Relevance

Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.

This article is protected by copyright. All rights reserved.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Map8s1
via IFTTT

Richard T. Johnson, 1931-2015

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1SVegUK
via IFTTT

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations

Abstract

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Z6a6gu
via IFTTT

Oral squamous cell carcinoma: Key clinical questions, biomarker discovery, and the role of proteomics

Publication date: March 2016
Source:Archives of Oral Biology, Volume 63
Author(s): Uzma Urooj Malik, Shamshad Zarina, Stephen R. Pennington
BackgroundThe molecular and cellular mechanisms underlying the pathogenesis of oral squamous cell carcinoma (OSCC) are relatively poorly understood and remain a subject of significant importance. However, it is well established that OSCC is associated with a variety of risk factors and notably, the high incidence rates of OSCC found in developing countries are attributable to exposure to different forms of smokeless tobacco. Despite this, the way these factors contribute to the disease pathogenesis and, in particular, the transformation from oral premalignant lesions (OPLs) to primary tumor remains unknown. Recent developments in 'omics' technologies hold promise for deciphering these mechanisms through the discovery of key molecular and cellular regulatory pathways which are involved in disease progression.ObjectiveThe aim of this critical review is to outline, through the current etiological, epidemiological, and molecular understanding of OSCC highlighting the role of key signaling pathways in the disease, and discuss the opportunities offered by recent proteomics strategies to identify potential biomarkers and novel mechanisms for OSCC.Results and conclusionsThe recent consolidation of methods for LC-MS/MS based protein expression analysis mass spectrometry and targeted protein measurement should support the discovery of new drug targets and diagnostic methods. We suggest that such studies will be most effective if they are focused on addressing the key clinical issues in the progression and treatment of this prevalent disease.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/21YREbK
via IFTTT