Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation

The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with pathologic, psychological, and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, among others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models have allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation.     

Differences in SLE disease activity between patients of Caucasian and South‐East Asian/Chinese background in an Australian hospital

Aim: We performed a semiprospective and retrospective review of all admissions to a single institution of systemic lupus erythematosus (SLE) patients, admitted due to active disease. The aim was to describe differences in disease activity as a cause of hospital admissions between patients originating from South‐East Asia/China (SAC) and Caucasians. Method: There were 210 patients admitted for active disease, with a total of 567 admissions for active SLE over a 16‐year period. Allowing for patients who had left our database, there was a total of 3415 patient years of observation. Results: Patients from SAC with a flare requiring admission presented earlier in their disease course and with more active disease than did Caucasians (median SLE Disease Activity Index 13 vs. 8, P= 0.002). They had longer inpatient stays (7 vs. 5 days P = 0.03). There was a trend to higher rates of re‐presentation to hospital for flare (59% in SAC patients vs. 41% in Caucasians, P = 0.09) with more subsequent admissions (3 vs. 2 P = 0.06) despite a shorter period of observation. Conclusions: South‐East Asian/Chinese were more likely to be diagnosed with class III/IV glomerulonephritis and require cyclophosphamide both at presentation and subsequent admissions. More patients from SAC were readmitted to hospital for severe central nervous system disease after their first hospital admission. In this population, lupus patients had more severe flares and more frequently required admission for these than Caucasians.     

In vitro effects of detergent sclerosants on coagulation, platelets and microparticles.

OBJECTIVES: To investigate the in vitro effects of Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on clotting tests, clotting factors, platelets and microparticles. MATERIALS AND METHODS: Platelet rich (PRP) and platelet poor (PPP) plasmas were incubated with varying concentrations of STS and POL. Clotting tests, platelet/plasma turbidity, and microparticle studies were performed. Specimens were mixed with individual factor deficient plasmas and clotting factor activities were studied. RESULTS: STS at high concentrations (>0.3%) destroyed platelets, microparticles and the clotting factors V, VII and X. It prolonged all clotting tests including prothrombin time (PT), activated partial thromboplastin time (APTT), non-activated partial thromboplastin time (NAPTT), thrombin time (TT), factor Xa clotting time (XACT) and surface activated clotting time (SACT). Higher concentrations of POL were required to achieve some anticoagulant activity. Low sclerosant concentrations shortened XACT and SACT, and induced release of procoagulant platelet derived microparticles. Increased exposure time resulted in increased procoagulant activity. STS at concentrations higher than 0.5% precipitated a complex containing apolipoprotein b and fibrinogen. CONCLUSIONS: Detergent sclerosants affect the clotting mechanism by interfering with clotting factor activities, procoagulant phospholipids and platelet derived microparticles. STS has more anticoagulant activity than POL in high concentrations. Low concentration sclerosants demonstrate procoagulant activity.     

Challenges and opportunities of nursing care in special-needs shelters.

Hurricanes Katrina and Rita forced many individuals along the coast of Texas and Louisiana to seek shelter inland. Among the evacuees were residents with special needs and residents of nursing homes and group homes caring for mentally retarded and physically disabled persons. Many nurses volunteered to provide health care for those in need. This article discusses challenges and opportunities that were encountered by nurses volunteering in special-needs shelters. Issues related to human and physical resources, patient care, and confidentiality are discussed including lessons learned. As nurses who cared for evacuees in the shelter, it is hoped some of the lessons learned can be utilized in future disasters.     

Impact of automatic orders to discontinue vancomycin therapy on vancomycin use in an antimicrobial stewardship program.

We examined the possible unintended consequences of a 72-hour automatic order to discontinue vancomycin therapy in an antimicrobial stewardship program (ASP). Of 120 patients, 11 had vancomycin therapy discontinued at 72 hours without a call to the ASP, and 7 experienced a treatment interruption of 6-36 hours. All discontinuation of therapy was considered appropriate, and the 7 treatment interruptions did not have clear clinical consequences. Only one-third of patients had ASP stickers that warned of impending discontinuation of vancomycin therapy placed appropriately in the medical record.