Treatment for Pulmonary Hypertension of Left Heart Disease

OPINION STATEMENT: Pulmonary hypertension (PH) secondary to left heart disease is a largely underestimated target of therapy. Except for a specific focus on PH consequences in patients with advanced heart failure (HF) receiving a left ventricular mechanical assist device or candidates for transplantation, prevention and treatment of initial subclinical forms of PH are not considered a priority in the management of this chronic disease population. Nonetheless, there is recent growing evidence supporting a clinical and prognostic role of PH in the elderly and in HF with preserved ejection fraction (pEF). Studies have defined PH-HFpEF as a new entity typically defining the evolving nature of disease. Although the prevalence of PH in these populations is not well-defined, the potential for effective pharmacological approaches that might impact the natural history of the disease starting from earlier stages is promising. However, it should be recognized that pharmacological studies performed to date with traditional pulmonary vasodilators in cohorts with HF and left-sided PH have not been positive, primarily because of concomitant systemic hypotension and hepatic side effects. This evidence along with the lack of studies specifically performed in the elderly and HFpEF often lead Guidelines to give neutral recommendations or even arbitrary assumptions. Recent availability of selective well-tolerated pulmonary vasodilators, such as phosphodiesterase type 5 (PDE5) inhibitors, however, seem to offer a solid background for treating left-sided PH at both early and later stages of the disease process.     

‘I've Been Walking on Eggshells All My Life’: Fibromyalgia Patients' Narratives About Experienced Violence and Abuse

According to earlier research, the prevalence of violence and abuse in the life history of patients with chronic widespread pain and fibromyalgia seems to be high in comparison with other pain patients and healthy controls. The purpose of the present study was to explore how experiences of violence and abuse are expressed and reflected on and how the causes and consequences of violence are interpreted by female patients with a long history of fibromyalgia. The data were drawn from narrative interviews of 11 women who had earlier participated in a fibromyalgia‐specific rehabilitation course. The findings are presented through three main themes: loss of self‐esteem, physical and mental bruises, and loss of womanhood. The onset of fibromyalgia was perceived as an inevitable result of physical or mental trauma. In conclusion, the narrated life stories indicated that violence is still hidden behind a wall of silence and non‐interference in our society. The devastating mental and physical consequences of violence in different forms may be carried by the individual for years, even decades. Understanding any exposure to violence that a patient has endured may help healthcare professionals to understand the individual's health behaviour and any possible reluctance to undergo treatment and rehabilitation. Copyright © 2015 John Wiley & Sons, Ltd.     

A low-affinity human granulocyte-macrophage colony-stimulating factor/murine erythropoietin hybrid receptor functions in murine cell lines

To identify domains in hematopoietic growth factor receptors that are important for signal transduction, a hybrid receptor (GMER) was constructed by splicing the DNA of the entire extracellular and transmembrane domains of the human granulocyte-macrophage colony- stimulating factor (GM-CSF) receptor alpha 2 subunit (GMR) to the cytoplasmic domain of the murine erythropoietin receptor (mEpoR). The hybrid receptor was introduced into the interleukin-3 factor-dependent murine hematopoietic cell line Ba/F3. Cells that expressed high receptor numbers were selected by cell sorting using phycoerythrin- labeled human GM-CSF. Immunoprecipitation of GMER from Ba/F3 cells showed a band with an Mr of 105,000 daltons. Human GM-CSF binding to Ba/F3 cells that expressed GMER showed a kd of 3.0 nmol/L and 475 binding sites/cell, while the same cells that expressed GMR had 300 sites/cell and a kd of 3.5 nmol/L. The proliferative response to GM-CSF of Ba/F3 cells that expressed GMER showed 1/2 maximal cell growth (as measured by 3H-thymidine incorporation) at a GM-CSF concentration of 2.5 x 10(-8) mol/L. When cultured in human GM-CSF, Ba/F3-GMER cells expressed cell surface glycophorin. Similar results were obtained with Ba/F3 cells transfected with the mEpoR and cultured in erythropoietin. Expression of GMR plus the human GM-CSF receptor beta chain in the same cell line also resulted in human GM-CSF stimulated proliferation; however, cell surface glycophorin was not detected. These data show that a low-affinity GM-CSF/Epo hybrid receptor can promote GM-CSF- dependent proliferation and can induce the expression of glycophorin, an erythroid-specific protein.     

Fixed and adjustable dose asthma action plans based on combination therapy: a pilot study

OBJECTIVE: The use of combination inhaled corticosteroid/long-acting beta-agonist therapy within the framework of a self-management plan has yet to be investigated. Methodology: In this randomized open-label study, 69 adult asthmatic patients taking >or= 1,000 microg per day of beclomethasone dipropionate (BDP) or equivalent were treated for 3 months with Symbicort Turbuhaler (200 microg budesonide/6 microg formoterol). Patients were assigned to one of two self-management plans, based on either a fixed or adjustable dose regimen. The primary outcome variable was episode-free days. RESULTS: Both regimens resulted in good asthma control, at least comparable to that obtained with previous high dose inhaled corticosteroid therapy. There were no significant differences in clinical outcome measures between the regimens. The mean (+/- SD) usage of Symbicort was similar for the fixed and adjustable dose regimens (3.8 +/- 0.68 vs 3.6 +/- 1.54 puffs per day, respectively). CONCLUSION: We conclude that Symbicort is effective when administered as either a fixed or adjustable dose regimen as part of a self-management plan.     

A Form of Hereditary Persistence of Fetal Haemoglobin Characterized by Uneven Cellular Distribution of Haemoglobin F and the Production of Haemoglobins A and A2 in Homozygotes

S ummary . Thirteen members of a British family were found to have elevated levels of haemoglobin F (Hb F) which segregated into two groups with mean values of 19.8±0.52% and 8.9±3.1% respectively. Genetic data indicate that the individuals in the former group are probably homozygous, and those in the latter group heterozygous, for the gene causing persistent Hb-F production. There is a significant reduction in the level of Hb A₂ in the homozygotes. The Hb F is hcterogeneously distributed among the red cells of each of the affected family members. In each case the haematological findings are normal and biosynthetic studies indicate balanced globin-chain synthesis. Chemical studies indicate that the Hb F consists mainly of the Ay type together with a small (c 10%) but significant amount of the Gy type in both homozygotes and heterozygotes. The other red-cell proteins and antigens are of the adult variety in all affected family members. The condition differs from previously described forms of hereditary persistence of fetal haemoglobin by virtue of the heterogeneous distribution of the Hb F and the presence of β and δ-chain synthesis in homozygotes. Its possible basis as a controller-gene mutation is discussed.