The role of endothelial enzymes NOS, VAP-1 and CD73 in acute lung injury

Acute lung injury (ALI) is a syndrome of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that is not caused by left atrial hypertension. Since there is no effective treatment available, this frequent clinical syndrome significantly contributes to mortality of both medical and surgical patients. Great majority of the patients with the syndrome suffers from indirect ALI caused by systemic inflammatory response syndrome (SIRS). Sepsis, trauma, major surgery and severe burns, which represent the most common triggers of SIRS, often induce an overwhelming inflammatory reaction leading to dysfunction of several vital organs. Studies of indirect ALI due to SIRS revealed that respiratory dysfunction results from increased permeability of endothelium. Disruption of endothelial barrier allows extravasation of protein-rich liquid and neutrophils to pulmonary parenchyma. Both under normal conditions and in inflammation, endothelial barrier function is regulated by numerous mechanisms. Endothelial enzymes represent one of the critical control points of vascular permeability and leukocyte trafficking. Some endothelial enzymes prevent disruption of endothelial barrier by production of anti-inflammatory substances. For instance, nitric oxide synthase (NOS) down-regulates leukocyte extravasation in inflammation by generation of nitric oxide. CD73 decreases vascular leakage and neutrophil emigration to inflamed tissues by generation of adenosine. On the other hand, vascular adhesion protein-1 (VAP-1) mediates leukocyte trafficking to the sites of inflammation both by generation of pro-inflammatory substances and by physically acting as an adhesion molecule. The aims of this study were to define the role of endothelial enzymes NOS, CD73 and VAP-1 in acute lung injury. Our data suggest that increasing substrate availability for NOS reduces both lung edema and neutrophil infiltration and this effect is not enhanced by concomitant administration of antioxidants. CD73 protects from vascular leakage in ALI and its up-regulation by interferon-β represents a novel therapeutic strategy for treatment of this syndrome. Enzymatic activity of VAP-1 mediates neutrophil infiltration in ALI and its inhibition represents an attractive approach to treat ALI.

Airway surgery for obstructive sleep apnea and partial upper airway obstruction during sleep

This study analyzed the feasibility and efficacy of surgical therapies in patients with sleep-disordered breathing ranging from partial upper airway obstruction during sleep to severe obstructive sleep apnea syndrome. The surgical procedures evaluated were tracheostomy, laser-assisted uvulopalatoplasty (LUPP) and uvulopalatopharyngoplasty (UPPP) with laser or ultrasound scalpel. Obstructive sleep apnea and partial upper airway obstruction during sleep were measured with the static charge-sensitive bed (SCSB) and pulse oximeter. The patients with severe obstructive sleep apnea syndrome were treated with tracheostomy. Palatal surgery was performed only if the upper airway narrowing occurred exclusively at the soft palate level in patients with partial upper airway obstruction during sleep. The ultrasound scalpel technique was compared to laser-assisted UPPP. The efficacy of LUPP to reduce partial upper airway obstruction during sleep was assessed and histology of uvulopalatal specimen was compared to body fat distributional parameters and sleep study findings. Tracheostomy was effective therapy in severe obstructive sleep apnea. Partial upper airway obstruction and arterial oxyhemoglobin desaturation index during sleep decreased significantly after LUPP. The minimal retropalatal airway dimension increased and soft palate collapsibility decreased at the level where the velopharyngeal obstruction had occurred before the surgery. Ultrasound scalpel did not offer any significant benefits over the laser-assisted technique, except fewer postoperative haemorrhage events. The loose connective tissue as a manifestation of edema was the only histological finding showing correlation with partial upper airway obstruction parameters of SCSB. Tracheostomy remains a life-saving therapy and also long-term option when adherence to CPAP fails in patients with obstructive sleep apnea syndrome. LUPP effectively reduces partial upper airway obstruction during sleep provided that obstruction at the other levels than the soft palate and uvula were preoperatively excluded. Technically the ultrasound scalpel or laser surgeries are equal. In patients with partial upper airway obstruction the loose connective tissue is more important than fat accumulation in the soft palate. This supports the hypothesis that edema is a primary trigger for aggravation of upper airway narrowing during sleep at the soft palate level and evolution towards partial or complete upper airway obstruction during sleep.

Foot Health In Older People - Development of a preventive, evaluative instrument for nurses

Foot health is a part of overall health in every age group and its importance increases during ageing. Health care professionals are in a vital position for preventing foot health problems, and identifying and caring them in older people. Despite the rather high number of studies conducted in the field of foot health in older people, reliable and valid nurse-administered foot health assessment instruments seem to be lacking. By identifying foot health in older people, it is possible to develop nursing interventions to enhance safe, independent living at home. The purpose of this three-phase study was to develop an instrument to assess the level of foot health in older people and evaluate foot care practices from the perspective of older people themselves and nurses in home care. The ultimate goal is to prevent foot health problems by increasing the attention paid to older people’s feet and recognizing those foot health problems which need further care; thus not focus on different foot health problems. The study was conducted in different phases and contexts. In phase 1, a descriptive design with a literature review from the Medline (R) and CINAHL databases to explore foot health in older people and nurses’ role in foot health care and pre-post design intervention study in nursing home with nursing staff (n=16) and older residents (n=43) were conducted. In phase 2, a descriptive and explorative study design was employed to develop an instrument for assessing foot health in older people (N=651, n=309, response rate 47%) and explore the psychometrics of the instrument. The data were collected from sheltered housing and home care settings. Finally, in phase 3, descriptive and explorative as well as cross-sectional correlational survey designs were used to assess foot health and evaluate the foot self-care activities of older people (N=651, n=309, response rate 47%) and to describe foot care knowledge and caring activities of nurses (N=651, n=322, response rate 50%) in home care in Finland. To achieve this, the Foot Health Assessment Instrument (FHAI) developed in phase 2 was used; at the same time, this large sample also was used for the psychometric evaluation of the FHAI. The data analysis methods used in this study were content analysis, descriptive and inferential statistics including factor and multivariate analysis. Many long-term diseases can manifest in feet. Therefore, the FHAI, developed in this study consisted of items relating to skin and nail health, foot structure and foot pain. The FHAI demonstrated acceptable preliminary psychometric properties. A great deal of different foot health problems in older people were found of which edema, dry skin, thickened and discoloured toenails and hallux valgus were the most prevalent foot health problems. Moreover, many older people had difficulties in performing foot self-care. Nurses’ knowledge of foot care was insufficient and revealed a need for more information and continuing education in matters relating to foot care in older people. Instead, nurses’ foot care activities were mainly adequate, though the findings indicate the need for updating foot care activities to correspond with the evidence found in the field of foot care. Practical implications are presented for nursing practice, education and administration. In future, research should focus on developing interventions for older people and nurses to promote foot health in older people and to prevent foot health problems, as well as for further development of the FHAI.