Stereoselective and endothelium-independent action of nicardipine on the isolated porcine coronary artery

The qualitative and quantitative effects of the (+)-S and (-)-R enantiomers and of the racemic mixture of the Ca2+ channel antagonist, nicardipine, were compared on the isolated porcine coronary artery with intact and removed endothelium. All three forms of nicardipine inhibited the contractions induced by KCl (5-90 mM) in both vessel preparations. The potency (IC50) of the (+)-S and (-)-R enantiomers and of the racemic mixture was 6.6, 31.8 and 10.9 nM in the vessel with endothelium and 6.4, 41.9 and 9.8 nM in the vessel without endothelium. The parameters of the concentration-response curves for each form of nicardipine at a submaximal KCl (60 mM) concentration and the potency ratios between the two enantiomers ((+)-S/(-)-R) were not statistically significantly different (P>0.05) in the two vessel preparations. In conclusion, qualitatively, all three forms of nicardipine showed only Ca2+ channel antagonistic effects in both vessel preparations. Quantitatively, the inhibition of contraction was stereoselective, the (+)-S enantiomer being the most potent, and was endothelium-independent.     

Responsible implementation of expanded carrier screening

This document of the European Society of Human Genetics contains recommendations regarding responsible implementation of expanded carrier screening. Carrier screening is defined here as the detection of carrier status of recessive diseases in couples or persons who do not have an a priori increased risk of being a carrier based on their or their partners'' personal or family history. Expanded carrier screening offers carrier screening for multiple autosomal and X-linked recessive disorders, facilitated by new genetic testing technologies, and allows testing of individuals regardless of ancestry or geographic origin. Carrier screening aims to identify couples who have an increased risk of having an affected child in order to facilitate informed reproductive decision making. In previous decades, carrier screening was typically performed for one or few relatively common recessive disorders associated with significant morbidity, reduced life-expectancy and often because of a considerable higher carrier frequency in a specific population for certain diseases. New genetic testing technologies enable the expansion of screening to multiple conditions, genes or sequence variants. Expanded carrier screening panels that have been introduced to date have been advertised and offered to health care professionals and the public on a commercial basis. This document discusses the challenges that expanded carrier screening might pose in the context of the lessons learnt from decades of population-based carrier screening and in the context of existing screening criteria. It aims to contribute to the public and professional discussion and to arrive at better clinical and laboratory practice guidelines.It is estimated that there are more than 1300 recessively inherited disorders (autosomal and X-linked), whose symptoms range from the very mild to severe, cumulatively affecting at least 30 in every 10 000 children.^{1, 2} This means that approximately 1–2 in 100 couples are couples who are at risk of having a child affected with a recessive genetic condition.³ Currently, the standard practice is to offer carrier testing to individuals at adult age who have a family history of a particular recessive disease; to the partners and relatives of identified carriers, or to the partners of people with the disease. However, in this way, only a minority of carrier couples will be identified, since the majority of affected children are born to couples with no previous known family history, and only a minority of relatives in high-risk families request carrier testing.⁴ The document was prepared by members of the Public and Professional Policy Committee (PPPC) of the European Society of Human Genetics (ESHG) and approved by the ESHG Board on 6 September 2015. This document is also endorsed by the British Society for Genetic Medicine (BSGM) Board. A summary of this document with the recommendations will be published in print in the European Journal of Human Genetics.⁵ The below full version with extensive references is published online only.     

Pseudoexfoliation syndrome and asymptomatic myocardial dysfunction

Background The purpose of this study was to investigate the frequency of asymptomatic left ventricular dysfunction in patients with pseudoexfoliation syndrome.Methods Two-dimensional and pulsed Doppler echocardiography of transmitral flow was performed on 27 patients with pseudoexfoliation syndrome, aged 66.9±5.6 years, and 24 healthy volunteers aged 63.9±6.5 years. Left ventricular (LV) systolic contraction and ejection were assessed by LV ejection fraction (EF) and fractional shortening (FS). LV diastolic filling parameters tested were: early fast diastolic filling (E wave), late diastolic filling (A wave), ratio E/A, velocity time integral E wave (VTIE) and A wave (VTIA), their ratio (VTIE/VTIA), pressure at the end of filling (LVEDP) and a pulmonary capillary wedge pressure (PCWP).Results Systolic parameters EF and FS, diastolic filling parameters such as A, LVEDP and PCWP were not significantly different between patients with pseudoexfoliation syndrome and controls (P>0.05). A significant difference (P<0.05) was found with regard to the diastolic filling parameters: E (61.6±15.1 vs 83.7±21.4), ratio E/A (0.8±0.1 vs 1.1±0.2), VTIE (8.6±1.8 vs 9.8±1.9), VTIA (10.3±2.4 vs 7.8±1.6) and ratio VTIA/VTIE (1.2±0.2 vs 0.8±0.2).Conclusion Our study suggests the possibility of an association between patients with pseudoexfoliation syndrome and a discrete asymptomatic myocardial diastolic dysfunction.The authors have no proprietary or financial interest in any research or devices described in the presented study.     

In vitro study of the variable square pulse Er:YAG laser cutting efficacy for apicectomy

BACKGROUND AND OBJECTIVES: Variable square pulse (VSP) Er:YAG laser should be quicker than older Er:YAG lasers. The objectives were: (1) comparison of VSP laser and mechanical handpiece efficacy for apicectomy and (2) determination of optimal pulse width/energy/frequency combination. STUDY DESIGN/MATERIALS AND METHODS: Sixty extracted, single-rooted mature human teeth with round apical parts were instrumented, root filled, cleaned, and divided into four groups. Apical 2 mm of each root were apicectomized with mechanical handpiece and Er:YAG laser with three different settings (LaserA = 200 mJ/300 microseconds/ 8 Hz; LaserB = 200 mJ/100 microseconds/8 Hz; LaserC = 380 mJ/100 microseconds/20 Hz). Timing results were statistically compared. RESULTS: LaserC was the most efficient setting. Differences between groups were significant except between LaserC-Mechanical and LaserA-LaserC (P < 0.05). CONCLUSIONS: VSP Er:YAG laser used for apicectomy is slower by a factor of 7-31 than mechanical handpiece, but treatment outcome is acceptable. Optimal settings for apicectomy with VSP laser are 380 mJ/100 microseconds/20 Hz.     

The Incidence of Nontraumatic Phakic Rhegmatogenous Retinal Detachment in Split-Dalmatia County, Croatia

We studied the incidence of nontraumatic phakic rhegmatogenous retinal detachment (RRD) in a defined population of Split-Dalmatia County, Croatia. In this clinic-based study, 272 of a population of 465,947 developed RRD during an 11-year period (1988–1998). The annual incidence was, therefore, 5.3 per 100,000 population. The highest risk for RRD was between the ages of 60 and 69 years. This revised version was published online in July 2006 with corrections to the Cover Date.     

Cardiovascular effects induced by polymeric 3-alkylpyridinium salts from the marine sponge Reniera sarai

Water-soluble polymeric 3-alkylpyridinum salts (poly-APS), isolated from the marine sponge Reniera sarai, are natural products with promising biomedical applications. However, their ability to form non-specific cell membrane pores raises safety issues. Therefore, the aim of the present study was to investigate the direct toxic effects of poly-APS on the cardiovascular system. To study the impact of poly-APS toxicodynamics on vascular function, the relaxation and contraction responses of isolated rat thoracic aortas incubated in poly-APS solutions (0.01-10 μM) were tested. In addition, cardiac toxicity was studied by measuring coronary flow, lactate dehydrogenase release rate, left ventricular pressure, heart rate, and the duration of arrhythmias in isolated rat hearts perfused with poly-APS (0.001-1 μM). Poly-APS diminished endothelium-dependent relaxation and contraction in a concentration- and time-dependent manner. Endothelial function was affected earlier and to a greater extent than contractile responses. Likewise, in isolated hearts the most evident cardiotoxic effects were observed after perfusion with the highest concentration (1 μM) of poly-APS: compared to the control group the coronary flow and heart rate were diminished by 2.2- and 1.8-fold, while lactate dehydrogenase release rate and left ventricular pressure were increased by 7.8- and 2.2-fold (all P < 0.001). Further, poly-APS had evident proarrhythmogenic activity in a concentration-dependent manner. However, in the low concentration range (1-10 nM) poly-APS showed only minor toxicity. Our results confirmed the direct toxic effects of poly-APS on the rat cardiovascular system. Therefore, it seems reasonable to conclude that the use of poly-APS as therapeutic adjuvants has limited safety margins.     

Protective intramedullary fixation after harvest of an osteocutaneous radial free flap.

The osteocutaneous radial free flap, even after 30 years, is still considered to be the "workhorse" for head and neck reconstruction. A high incidence of donor site fractures has remained a major problem, however. The technique described here is a method developed for the prophylaxis of fractures of the donor site of the harvested radial bone and is based on a modification of the intramedullary Rush nail fixation. The data were collected from 18 patients in whom the radial forearm free flap had been used during reconstruction. None of the prophylactically-nailed radii fractured. The complications experienced with this technique are general complications, such as scarring of the forearm and dehiscence of the wound. This technique is simple, and has given excellent results. Aesthetic and functional results were comparable to those of other flaps used for reconstruction. We recommend this technique because of its simplicity, vascular safety, and cost effectiveness.     

Maternal Pre-Pregnancy Nutritional Status and Physical Activity Levels and a Sports Injury Reported in Children: A Seven-Year Follow-Up Study

Objective: Our aim was to analyze dose–response associations between maternal pre-pregnancy body mass index and physical activity levels with childhood sports injury rates. Methods: Participants included pre-pregnant mothers (n = 4811) and their children at the age of 7 years (n = 3311). Maternal anthropometry (height, weight, and body mass index), time spent in physical activity, and education level were recorded. All sports injuries were defined as injuries reported in the past year by the children at the age of 7 years. Results: Children whose mothers were overweight/obese in the pre-pregnancy period were 2.04 (OR = 2.04, 95% CI = 1.12–3.71) times more likely to report a sports injury at the age of 7 years. Underweight mothers exhibited a 74% decrease in the odds of their children reporting a sports injury at follow-up (OR = 0.26, 95% CI = 0.10–0.68). Finally, an increase in maternal physical activity across the last three quartiles was associated with a lower odds of sports injuries. Conclusions: The risk of reporting a sports injury was greater for children whose mothers were overweight/obese in the pre-pregnancy period. However, there was a lower risk with both maternal underweight status and increasing minutes of physical activity.     

Educational initiatives and training for paediatric rheumatology in Europe

The Paediatric Rheumatology European Society (PReS) has over many years, developed a portfolio of educational activities to address increasing educational needs of workforce and support young clinicians to acquire skills to develop new knowledge and deliver clinical care in the future. These educational activities aim to facilitate growth of paediatric rheumatology and ultimately improve the clinical care for children and families. This article describes the current portfolio of PReS educational activities and their relevance to the international paediatric rheumatology community.