Mannan-binding protein and complement dependent opsonization in alcoholic cirrhosis

Mannan-binding protein is synthesized by the liver and functions in first-line host defence by opsonizing mannose-rich microorganisms due to activation of the classical complement pathway independent of Clq, and by an intrinsic ability to opsonize and mediate phagocytosis. We have investigated whether the increased susceptibility to bacterial infections in patients with cirrhosis could be explained by low plasma concentrations of mannan-binding protein and impaired complement-dependent opsonization. We examined 51 patients with compensated alcoholic cirrhosis, 34 who were decompensated and 16 healthy controls. Irrespective of group, we found a significant correlation (p<0.05) between plasma mannan-binding protein concentration and deposition of the complement opsonin C4 on mannan from baker's yeast. In contrast to what was expected, this kind of opsonization and plasma levels of mannan-binding protein were significantly increased in the patients with decompensated cirrhosis (p=0.01 and p=0.007, respectively). A significant correlation (0<0.05) was found between mannan-binding protein and erythrocyte sedimentation rate, fibrinogen and haptoglobin in these patients. Though the correlations were weak (rho=0.49, rho=0.48 and rho=0.40, respectively), the elevated levels of mannan-binding protein in the patients with decompensated cirrhosis may reflect an acute phase reaction. It is concluded that plasma levels of mannan-binding protein are increased in patients with decompensated cirrhosis and that complement-dependent opsonization of mannan does not seem to be compromized in patients with alcoholic cirrhosis.     

Risk factors for asthma in adult twins

Introduction: This PhD thesis was conducted at the Respiratory and Allergy Research Unit, Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark. Objective: This study was conducted in a population of adult twins to: (i) determine the incidence of asthma; (ii) identify the risk factors for asthma; and (iii) estimate to what extent genetic and environmental factors influence asthma, wheeze, rhinitis, positive skin‐prick test (posSPT) and airway hyper‐responsiveness (AHR). Materials and Methods: The study population was based on the twin cohorts born between 1953 and 1982 that were ascertained from the nationwide Danish Twin Registry. Questionnaire data on multiple traits including asthma and possible risk factors for asthma was collected in 1994 and 2002, defining a population of 19 349 subjects (6090 intact twin pairs) at risk of new asthma. Furthermore, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co‐twins reported a history of asthma at the 2002 questionnaire, were clinically examined. Results: The incidence of asthma was 4.5 and 6.4 per 1000 person‐years, respectively, among males and females (Odds Ratio (OR) = 1.49, P < 0.001). There was a positive association between increasing body mass index (BMI) and risk of asthma for both sexes (OR = 1.05 per unit, P < 0.001). A history of hay fever (OR = 4.2 for males and OR = 3.7 for females, P < 0.001), eczema (OR = 3.5 for males and OR = 2.0 for females, P < 0.001) and both (OR = 6.9 for males and OR = 8.0 for females, P < 0.001) were significant predictors of asthma. Physical exercise was weakly associated with asthma (OR for inactivity = 0.35, P = 0.02), whereas smoking and educational status was not significantly associated with asthma. There was a high genetic similarity between asthma and wheeze (genetic correlation, ρ_A = 0.96), asthma and rhinitis (ρ_A = 0.94), wheeze and rhinitis (ρ_A = 0.95), wheeze and AHR (ρ_A = 0.85), and rhinitis and posSPT (ρ_A = 0.92), whereas lower genetic correlations were observed between rhinitis and AHR (ρ_A = 0.43) and between AHR and posSPT (ρ_A = 0.59). Traits with a high degree of environmental sharing were asthma and wheeze (environmental correlation, ρ_E = 0.82), rhinitis and posSPT (ρ_E = 0.92), and wheeze and posSPT (ρ_E = 0.71), whereas lower environmental correlations were observed between asthma and rhinitis (ρ_E = 0.19) and between wheeze and rhinitis (ρ_E = 0.25). Conclusions: The incidence of asthma in adulthood is high, especially among females. In both sexes, increasing levels of BMI increase the risk of asthma. A substantial portion of adult‐onset asthma is preceded by hay fever and eczema. Asthma, wheeze, rhinitis, AHR and posSPT share, to a large extent, a common genetic aetiology. In particular, asthma and rhinitis are genetically similar, but environmentally distinct. Furthermore, genetic factors mainly explain the co‐occurrence of asthma and posSPT, and rhinitis and posSPT, whereas asthma, but not rhinitis, is closely genetically related to AHR. Finally, asthma and posSPT, and rhinitis and posSPT show similar environmental architectures. These results provide new insights into the aetiology of asthma and may be used to guide the choice of traits for genetic linkage analysis.     

HV interval in calcific aortic stenosis. Relation to left ventricular function and effect of valve replacement

Intracardiac electrography and 24 hour ambulatory electrocardiographic monitoring were carried out in 20 patients with calcific aortic stenosis (mean pressure gradient 86 mm Hg) to investigate (a) the role of bradycardia and tachycardia in the pathogenesis of syncope in aortic stenosis, (b) the relation between haemodynamic data and electrophysiological abnormalities, and (c) whether valve replacement corrects electrophysiological abnormalities. Intracardiac electrograms showed impaired sinus node function in five patients and a prolonged HV interval (greater than or equal to 50 ms) in 11 but there was no difference in the findings of 13 patients with syncope and seven without. Ambulatory monitoring showed short pauses in three patients and brief episodes of tachycardia in four, but there was no difference in the findings of patients with and without syncope. The HV interval correlated inversely with the left ventricular ejection fraction, whereas no correlation was found between the HV interval and the pressure gradient. Nine patients were re-evaluated 15 months after aortic valve replacement. No change was found in sinus node function, but the HV interval had increased by 7.8 ms. It is concluded that in calcific aortic stenosis neither bradycardia nor tachycardia is shown to be a frequent cause of syncope, a prolonged HV interval is a frequent finding and further prolongation occurs after valve replacement, and contractility and conductivity appear to deteriorate in parallel.     

The Intentional Differences: A Qualitative Study of the Views and Experiences of Non-peer Mental Health Providers on Working Together with Peer Support Colleagues in Mental Health

Community Mental Health Journal - The study reports the results of a qualitative study on the views and experiences of non-peer mental health providers on working together with peer colleagues in...     

Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non‐classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.     

Cold urticaria – What we know and what we do not know

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.     

Characteristics of culprit lesion in patients with non-ST-elevation myocardial infarction and improvement of diagnostic utility using dual energy cardiac CT

Aims

The aim of the study was to identify the characteristics of the culprit lesions compared to non-culprit lesions in patients with non-ST-elevation-myocardial infarction using dual energy computed tomography (DECT).

Methods and results

In 29 patients, we identified 29 culprit lesions and 227 non-culprit lesions.

Quantitative values such as the effective atomic number (effective-Z) and Hounsfield Units (HU) values were measured. Furthermore, all the lesions were characterised using characteristics such as composition (non-calcified, predominantly-non-calcified, predominantly-calcified, or calcified), presence of spotty calcification, remodelling index, and napkin ring sign.

The mean effective-Z and HU values were significantly lower in culprit lesions than in non-culprit lesions (8.99?±?1.21 vs 9.79?±?1.52; p?=?0.0066 and 87.41?±?84.97 vs. 154.45?±?176.13; p?=?0.0447). The culprit lesions had a higher frequency of non-calcified plaques and predominantly non-calcified plaques, and were with a greater presence of napkin ring signs in comparison with non-culprit lesions. There were no differences in the presence of spotty calcification or remodelling index.

By adding effective-Z to plaque characteristics such as non-calcified, positive remodelling, spotty calcification, and napkin rings we observed a significant increased sensitivity of detecting culprit lesions (65.5% vs.44.8%), but no significant changes in area under curve (AUC).

Conclusion

The use of DECT adds new information of the plaque composition expressed by the effective-Z, which differs significantly in culprit lesions in comparison with non-culprit lesions. The use of the effective-Z improves the diagnostic sensitivity in detection of culprit lesions.