Clinical similarities among bradykinin-mediated and mast cell-mediated subtypes of non-hereditary angioedema: a retrospective study

Background

Non-hereditary angioedema (non-HAE) is characterized by local swelling due to self-limiting, subcutaneous or submucosal extravasation of fluid, and can be divided into three subtypes. These subtypes are believed to have different pathophysiological backgrounds and are referred to in recent guidelines as bradykinin-mediated (e.g. caused by angiotensin-converting-enzyme-inhibitors), mast cell-mediated (e.g. angioedema with wheals) or idiopathic (cause unknown). Bradykinin-mediated subtypes are more closely related to hereditary angioedema than the other forms. Because clinical features of these non-HAE subtypes have not been studied in detail, we have looked at the clinical characteristics of symptoms and potential differences in clinical presentation of bradykinin-mediated and mast cell-mediated angioedema (AE) subtypes.

Methods

A questionnaire was sent to patients presenting with AE at our tertiary outpatient clinic to document clinical characteristics, potential triggers and location of AE. The severity of AE attacks was analysed using visual analogue scales (VAS).

Results

The questionnaire was returned by 106 patients, of which 104 were included in the analysis. AE with wheals, idiopathic AE, and drug-associated AE occurred in 64 (62%), 25 (24%) and 15 patients (14%) respectively. Most patients (62%) reported prodromal symptoms while 63% reported multiple locations for an attack. Face and oropharynx were the main locations of AE attacks of any subtype while swelling was the symptom most frequently reported as severe. Overall severity of the last attack was indicated as severe by 68% of the patients. There were no differences between the subgroups.

Conclusion

This similarity in clinical presentation raises the possibility that ACEi-induced, mast cell-mediated and idiopathic AE share common pathways.

Electronic supplementary material

The online version of this article (doi:10.1186/s13601-015-0049-8) contains supplementary material, which is available to authorized users.     

Binding of the adhesion and pathogen receptor DC-SIGN by monocytes is regulated by the density of Lewis X molecules

Soluble DC-SIGN (CD209) bind unsialylated Lewis X epitopes that are abundantly expressed on neutrophils. Due to the low expression of unsialylated Lewis X epitopes on monocytes, no binding of soluble DC-SIGN molecules was seen. In contrast, beads coated with multiple DC-SIGN molecules show a high percentage of binding to monocytes. The increased number of DC-SIGN molecules present on the beads enable multivalent interactions between the DC-SIGN molecules and the scarce Lewis X epitopes present on monocytes. Increased expression of unsialylated Lewis X epitopes on monocytes after neuraminidase treatment coincided with enhanced binding to soluble DC-SIGN. Multiple unsialylated Lewis X epitopes in close proximity of each other are now able to interact multivalently to soluble DC-SIGN. From these findings, we conclude that firm interactions between DC-SIGN and monocytes can be established by either increasing the density of DC-SIGN molecules at the cell surface or by increasing the number of Lewis X epitopes. Regulating the number of ligands endows monocytes with the capacity to modulate binding to DC-SIGN. This may result in a bi-directional cross-talk between DC and monocytes, to modulate innate and/or adaptive immune responses.     

Deficiency of pyrimidine 5′-nucleotidase in human leukocytes

Summary Both erythrocytes and leukocytes from a patient with erythrocyte pyrimidine 5-nucleotidase (P5N) deficiency were shown to contain increased amounts of pyrimidine nucleotides. These findings suggested that the leukocytes were also deficient for P5N. Measurement of the P5N activity in lysates from lymphocytes or granulocytes, in the presence of inhibitors for non-specific 5-nucleotidase or alkaline phosphatase, indeed showed a deficiency for P5N in lymphocytes and granulocytes of the patient with erythrocyte P5N deficiency. However, the P5N deficiency in the leukocytes did not cause clinical disturbances in addition to the weak haemolytic anaemia.     

International application of health literacy measures: Adaptation and validation of the newest vital sign in The Netherlands

Objective

The newest vital sign assesses individual reading and numeracy skills. The aim of this study was to create a Dutch version (NVS-D) and to assess its feasibility, reliability, and validity in The Netherlands.

Methods

We performed a qualitative study among experts (n = 27) and patients (n = 30) to develop the NVS-D and to assess its feasibility. For validation, we conducted a quantitative survey (n = 329). Reliability was assessed by Cronbach's alpha. Construct validity was examined by analyzing association patterns. Receiver operating characteristic (ROC) curves determined optimal cut-off scores.

Results

Cronbach's alpha was 0.76. In accordance with a priori hypotheses we found strong associations between NVS-D, general vocabulary, prose literacy and objective health literacy, and weaker associations between NVS-D and subjective health literacy. A score of ≥4 out of 6 best distinguished individuals with adequate versus inadequate health literacy.

Conclusion

The results suggest that the NVS-D is a reliable and valid tool that allows international comparable health literacy research in The Netherlands.

Practice implications

The NVS-D can be applied in research on the role of health literacy in health and health care, and the development of interventions. The methods can be applied in cross-cultural adaptation of health literacy measures in other countries.     

The potential for estradiol and ethinylestradiol to sorb to suspended and bed sediments in some English rivers

The endocrine-disrupting impact of steroid estrogens on fish will be strongly influenced by their distribution between sediment and water. Laboratory studies were performed to investigate the potential for sorption of 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) to bed and suspended sediments taken from five British rivers. Sediment material was collected from the Rivers Aire and Calder (located in urban and industrialized areas in Yorkshire, UK), the River Thames (at a relatively rural site in Oxfordshire, UK), and from the estuaries of the Rivers Tees and Tyne. Using anaerobic conditions to inhibit biodegradation, it was found that 80 to 90% of binding to bed sediments was complete within 1 d, but that an equilibrium had not been reached after 2 d. Bed sediments gave distribution coefficients (Kd) ranging from 4 to 74 L/kg for E2 and from 8 to 121 L/kg for EE2 for samples taken over a range of seasons and locations. Sorption to suspended sediment gave Kd values ranging from 21 to 122 L/kg for E2 and 19 to 260 L/kg for EE2. However, these Kd values suggest less than 1% removal of the steroid estrogens from the aqueous phase given the ambient suspended sediment concentration. In the bed sediments, higher Kd values were associated with smaller particle size and higher organic carbon content. In most cases, the Kd values obtained for EE2 were higher than those for E2 by a factor of up to three.