Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Improving the role of echocardiography in studying the right ventricle of repaired tetralogy of Fallot patients: comparison with cardiac magnetic resonance

Right ventricular (RV) evaluation represents one of the major clinical tasks in the follow-up of repaired tetralogy of Fallot patients (rToF) with pulmonary valve regurgitation, as both severe RV dilatation and dysfunction are key factors in defining the need of pulmonary valve replacement. The aim of our study was to report the diagnostic accuracy of echocardiography in the identification of rToF patients with severely dilated and/or depressed RV as compared to cardiac magnetic resonance (CMR). Among our patients with rToF, a subgroup of 95 (17.6?±?6.8 years; 60% male), who underwent right ventricular qualitative and quantitative evaluation with CMR following echocardiographic suspicion of severe dilation/dysfunction, were included in the analysis. When comparing echocardiographic RV functional parameters to CMR findings, we found no association between CMR-ejection fraction (EF) and either tricuspid annulus plane systolic excursion (TAPSe) nor tissue Doppler systolic tricuspid excursion velocity (all p?=?ns). In contrast RVFAC was strongly associated with CMR-EF (r?=?0.44; p?<?0.01) as well as to longitudinal components of RV mechanics including tissue Doppler s′ (r?=?0.40; p?<?0.01) and TAPSE (r?=?0.36; p?<?0.01). When comparing echocardiographic and CMR structural parameters of the RV, we found that CMR RV volume was strongly related to echocardiographic measurements of RV end diastolic area (from the 4 chamber apical view) and with proximal parasternal short axis right ventricle outflow-dimension. Accordingly a regression model was derived from multiple regression analysis, which allows a more accurate estimate of CMR RV volume from echocardiography (r²?=?0.59, p?<?0.001). Our study demonstrates a significant, although imperfect, correlation between echocardiographic and CMR RV functional and geometrical parameters. Combining echocardiographic measures of RV inflow and RV outflow, we deliver a simple formula to estimate CMR-RV volume, improving the echocardiographic accuracy in RV volume quantification.     

What Happens at a Dental Surgery When the Patient is a Child with Autism Spectrum Disorder? An Italian Study

Oral health care can be a difficult experience for a child with Autism Spectrum Disorder (ASD), for their family and for the dentist. The purpose of this study is to provide an understanding of the challenges experienced by the three aforementioned figures during oral care treatment. A cohort of 275 parents of typical development children (TD), 57 parents of children with ASD (3–15 years old) and by 61 dentists, completed two different multiple choices questionnaires. The data obtained show a great difficulty in the treatment of children with ASD as seen by the dentists and by the parents. This is due to: caregivers’ demographic issues; difficulties encountered before and during the dental examination; scarce presence of experts in ASD treatment.

     

The asthma knowledge and perceptions of older Australian adults: Implications for social marketing campaigns

Objective

The purpose of this research is to gain an understanding of the asthma perceptions of older adults and identify gaps in their asthma knowledge.

Methods

In regional New South Wales, Australia, a stratified, random sample of 4066 adults, aged 55 years and over, both with and without an asthma diagnosis, completed a survey based on the Health Belief Model about asthma knowledge and perceptions.

Results

Almost half of the sample had experienced symptoms of breathlessness in the past four weeks. Breathlessness was a predictor of lower health ratings and poorer mood. Older adults reported low susceptibility to developing asthma. The sample demonstrated poor knowledge of key asthma symptoms including shortness of breath, tightness in the chest and a cough at night.

Conclusion

There is a general lack of asthma awareness in this age group. This could result in not seeking medical help, and thus a reduced quality of life.

Practical Implications

Older adults should be made aware of key symptoms and the prevalence of asthma in the older adult population, and be empowered to take control of their respiratory health. Audience segmentation for an intervention should be based on recent experience of breathlessness and asthma diagnosis.     

Orbital volume and surface after Le Fort III advancement in syndromic craniosynostosis

There are no quantitative standards for the volumetric measurements of the orbital cavity after Le Fort III advancement. Computed tomography (CT) scan images have given the opportunity to compare with accuracy the real anatomic changes and potentially the functional improvements that resulted after a surgical treatment.Three-dimensional CT scan images processed by DICOM files in Dolphin 3D Software were used to assess orbital volume and surface in 12 subjects affected by craniofacial syndromic malformations treated with Le Fort III advancement. The preoperative (T0) and postoperative (T1: 6 months after surgery) three-dimensional craniofacial CT scans of the subjects were collected and retrospectively analyzed. Image segmentation of the anatomic orbital cavity and the three-dimensional graphic rendering were done by using the Dolphin Imaging Plus 11.0 software.The orbital volume was increased after surgery, with statistical significance, from 22,267 to 22,706.3 mm(3) in the right eye and from 26,511 mm(3) to 26,256.4 mm(3) in the left eye. The surface of both bony orbits had an expansion, which is statistically significant. In conclusion, this study showed that the orbital advancement in white subjects after Le Fort III advancement was significant and produced a significant augmentation of the orbital volume and surface area with correction of the ocular bulb proptosis.