Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Heart insufficiency in traumatic arteriovenous fistulas

Objective: To analyse the incidence, clinical presentation, and outcome of heart insufficiency in patients with chronic arteriovenous fistulas (AVF). Methodology: From 1991 to 2000 we treated 49 patients with traumatic AVF. The present study included 19 patients with AVF present for 6 months or longer, as it was presumed that these AVF will have an impact on cardiac overload. There were 16 male and three female patients with a mean age of 36 years (17–59). The time from injury to admission varied from 6 months to 33 years. Cardiological examination checked for dyspnoea and palpitation. ECG, chest X‐ray and ECHO‐cardiography were also performed. All AVF were deleted, magistral vessels reconstructed, non‐magistral obliterated, either surgically or by percutaneous embolization. Results: Mean follow up was 44.2 months (3–93). Serious heart insufficiency was seen in two patients only, with AVF in the subclavial vessels. Both suffered from serious heart disease prior to the therapeutic procedures that resulted in iatrogenic AVF, so it was difficult to connect heart insufficiency to the AVF alone. Despite surgical closure of AVF and intensive medical treatment, signs of heart insufficiency remained in both patients. Signs of cardiac overload were seen in six patients with long‐standing AVF in major vessels. Except for one patient who refused surgical closure of femoral AVF, the remaining five were symptom free for cardiac overload during the follow‐up period. Conclusion: In our series, heart insufficiency was an infrequent complication in long‐standing AVF, even when major vessels were involved.     

SPROUT,HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility

Summary Several components of a system for structure generation are now well developed. HIPPO is a program that characterises a receptor binding site for potential target sites within the cavity that can be used in de novo design. The target sites include simple and complex hydrogen bonds, covalent bonds and bonds to metal ions. The SPROUT program for structure generation consists of two main components: the first is skeleton generation, followed by atom substitution to convert the solution skeletons to molecules. A new method of skeleton generation is presented here, where part skeletons are grown outwards from each target site. The part skeletons are then connected together to form solution skeletons. Finally the CAESA program is described, that ranks the output from SPROUT according to ease of synthesis.     

SMI-32 parcellates the visual cortical areas of the marmoset

The distribution pattern of SMI-32-immunoreactivity (SMI-32-ir) of neuronal elements was examined in the visual cortical areas of marmoset monkey. Layer IV of the primary visual cortex (V1) and layers III and V of the extrastriate areas showed the most abundant SMI-32-ir. The different areal and laminar distribution of SMI-32-ir allowed the distinction between various extrastriate areas and determined their exact anatomical boundaries in the New World monkey, Callithrix penicillata. It is shown here that the parcellating nature of SMI-32 described earlier in the visual cortical areas of other mammals - including Old World monkeys - is also present in the marmoset. Furthermore, a comparison became possible between the chemoanatomical organization of New World and Old World primates' visual cortical areas.     

Effects of chemical mediators of anaphylaxis on ciliary function

We assessed the effects of selected chemical mediators of anaphylaxis on CBF in vitro. Ciliated epithelial cells were obtained from the trachea of conscious sheep with a cytology brush and suspended in a perfusion chamber containing KH. Ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of CBF. Prostaglandin E1 (10(-8) M to 10(-6) M), prostaglandin E2 (10(-10) M to 10(-6) M), and leukotriene-C4 (10(-8) M) increased CBF between 7% and 33%. Histamine caused ciliostimulation only at the relatively high concentrations above 10(-5) M (7% increase in CBF), whereas prostaglandin F2 alpha (10(-10) M and 10(-6) M) was without effect. In no preparation was ciliary discoordination observed. These findings indicate that several chemical mediators of anaphylaxis stimulate CBF and that the previously described impairment of mucociliary transport in stable allergic asthma or antigen-induced bronchoconstriction is probably not caused by a primary alteration of ciliary function.     

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background

Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%–1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents.

Methods

Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre.

Results

3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004).

Conclusions

The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.

     

Differentiation of Rhizomucor Species by Carbon Source Utilization and Isoenzyme Analysis

Nineteen Rhizomucor miehei and Rhizomucor pusillus isolates were assayed for their ability to utilize 87 various substrates as a single carbon source. Besides a difference in sucrose utilization, distinctive differences were found in the utilization of glycine, phenylalanine, and β-alanine. Five isoenzyme systems also proved useful for the determination of markers of distinctive value at a species level. Data were used to obtain information about the genetic polymorphism of these species: a high degree of variability was found among the R. pusillus isolates, whereas the group of R. miehei isolates was more homogeneous genetically.