Inhalation of nitric oxide inhibits ADP-induced platelet aggregation and alpha-granule release

To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s -1 ). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear.     

Type beta transforming growth factor and epidermal growth factor suppress the plasminogen activator activity in a human glioblastoma cell line

Summary In the human glioblastoma cell line, T-MG1, plasminogen activator activity (PA activity) was demonstrated by using the chromogenic substrate S-2251. Using monoclonal antibodies against human urokinase type PA (u-PA) and human tissue type PA (t-PA), only u-PA activity was found in T MG1, cell extracts. The u-PA activity in T-MG1, cells was suppressed in a dose-dependent manner by B TGF and EGF after 24 hours of exposure to these growth factors. Twenty units of B TGF caused a decrease in PA-activity of 80%, while 10 ng/ml EGF gave a decrease in PA-activity of 60%. The suppressive effects of B TGF and EGF were observed after 2 hours and 4 hours of incubation, respectively and sustained for at least 24 hours. The effects of B-TGF and EGF were not antienzymatic, but rather mediated through regulatory mechanisms. In view of the capacity of invasive growth of gliomas and the potential role of PA in invasive growth, the suppression of PA-activity in gliomas by B-TGF and EGF may be of importance.     

Parents' Involvement in Life-and-Death Decisions in Neonatal Intensive Care: Norwegian Attitudes

This article discusses the general view of parents' role in life-and-death decision-making concerning very premature infants in Norway. The article is based on one qualitative study with parents and a survey among Norwegian health personnel. Our findings show that both parents and health-care professionals are ambivalent with regard to the question of who should decide. Parents who have experienced life-and-death discussions concerning their premature infants emphasize that the physician's ability to communicate and to include them as decision-making partners are more important than the parents' right to an autonomous choice. These findings seem to be in line with the official Norwegian recommendations of the subject matter.     

Patient-reported outcomes and different approaches to urinary parameters in overactive bladder: what should we measure?

Overactive bladder (OAB) is highly prevalent and associated with considerable impact on patient health-related quality of life (HRQoL). Assessment of HRQoL can reveal the burden of disease and post-intervention improvement. This review aims to highlight the importance of HRQoL assessment and outline the tools available for use in clinical trials and real-world clinical practice. A number of validated measures of HRQoL specific to OAB have been developed, offering greater sensitivity and responsiveness over generic instruments. These condition-specific, multi-dimensional and single-item global questionnaires are particularly useful for the multiple and varied symptoms of OAB, as they reflect the patient’s needs, concerns and values. Measurements for lower urinary tract symptoms, e.g. bladder diaries, are being compared with HRQoL instruments to provide greater understanding of the disease and treatment from the patient’s perspective. Therapeutic interventions to improve OAB symptoms should also be evaluated for their effect on the patient’s HRQoL.     

Intraobserver and interobserver reliability of the three-dimensional ultrasound imaging of female urethral sphincter using a translabial technique

Introduction and hypothesis

The aim of the study was to assess the interobserver and intraobserver reliability of translabial 3D ultrasound imaging of the urethral sphincter in non-pregnant nulliparous asymptomatic women.

Methods

A study using a 3D translabial ultrasound on thirty-seven women was performed. Urethral sphincter parameters were measured by the same experienced clinician 2?weeks apart. Multiple axial cross-sectional areas at 1-mm distances were used to calculate urethral sphincter volumes. The same measurements were carried out by a second experienced clinician to assess the interobserver reliability.

Results

We found an excellent intraobserver reliability (interclass correlation coefficient, ICC >0.8) and good interobserver reliability (ICC >0.6).

Conclusion

The described technique using multiple axial cross-sectional areas at set distances and a translabial approach is a reliable and accurate tool in the evaluation of the urethral sphincter. This should be used instead of mathematical formulas as the urethral sphincter is not a uniform geometrical sphere. The technique and values reported may help clinicians in the assessment of women with lower urinary tract disorders.     

Osteoprotegerin is associated with hip fracture incidence: the Tromso Study

BACKGROUND: Osteoprotegerin (OPG) is a cytokine essential for the regulation of bone resorption, but large longitudinal studies on its relationship to fracture risk in humans are lacking. In this population-based study of 2740 men and 2857 post-menopausal women, it was examined whether serum OPG was associated with hip fracture incidence. The participants were followed for 15 years. METHODS: Baseline measurements included height, weight and serum OPG, and information about lifestyle, prevalent diseases and use of medication. RESULTS: Men with OPG in the highest quartile were 2.79-fold [95% confidence interval (CI) 1.34-5.82] more likely to have a hip fracture during follow-up, compared with those with OPG in the lowest quartile (P-trend over OPG quartiles ≤0.001, after adjustments for age and other confounders). In women not using post-menopausal hormone therapy (HT), the risk of hip fracture was 1.64-fold higher (95% CI 0.94-2.86) in the highest quartile compared with the lowest OPG quartile (P-trend over OPG quartiles?=?0.05). No relationship was found in post-menopausal women using HT (P-trend over OPG quartiles?=?0.23). CONCLUSIONS: In men, OPG was positively associated with the incidence of hip fracture. In post-menopausal women not using HT a similar, but weaker, relationship was found.