Royal Adelaide Hospital

About: Royal Adelaide Hospital is a healthcare organization based out in Adelaide, South Australia, Australia. It is known for research contribution in the topics: Population & Gastric emptying. The organization has 5830 authors who have published 10241 publications receiving 347876 citations. The organization is also known as: Adelaide Hospital & RAH.

New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management

Abstract: New oral anticoagulants (NOAC) are becoming available as alternatives to warfarin to prevent systemic embolism in patients with non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolism. An in-depth understanding of their pharmacology is invaluable for appropriate prescription and optimal management of patients receiving these drugs should unexpected complications (such as bleeding) occur, or the patient requires urgent surgery. The Australasian Society of Thrombosis and Haemostasis has set out to inform physicians on the use of the different NOAC based on current available evidence focusing on: (i) selection of the most suitable patient groups to receive NOAC, (ii) laboratory measurements of NOAC in appropriate circumstances and (iii) management of patients taking NOAC in the perioperative period, and strategies to manage bleeding complications or ‘reverse’ the anticoagulant effects for urgent invasive procedures.

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

Abstract: The DNA-damage response (DDR) pathways consist of interconnected components that respond to DNA damage to allow repair and promote cell survival. The DNA repair pathways and downstream cellular responses have diverged in cancer cells compared with normal cells because of genetic alterations that underlie drug resistance, disabled repair and resistance to apoptosis. Consequently, abrogating DDR pathways represents an important mechanism for enhancing the therapeutic index of DNA-damaging anticancer agents. In this review, we discuss the DDR pathways that determine antitumor effects of DNA-damaging agents with a specific focus on treatment outcomes in tumors carrying a defective p53 pathway. Finely tuned survival and death pathways govern the cellular responses downstream of the cytotoxic insults inherent in anticancer treatment. The significance and relative contributions of cellular responses including apoptosis, mitotic catastrophe and senescence are discussed in relation to the web of molecular interactions that affect such outcomes. We propose that promising combinations of DNA-damaging anticancer treatments with DDR-pathway inhibition would be further enhanced by activating downstream apoptotic pathways. The proposed rationale ensures that actual cell death is the preferred outcome of cancer treatment instead of other responses, including reversible cell cycle arrest, autophagy or senescence. Finally, to better measure the contribution of different cellular responses to anticancer treatments, multiplex in vivo assessments of therapy-induced response pathways such as cell death, senescence and mitotic catastrophe is desirable rather than the current reliance on the measurement of a single response pathway such as apoptosis.

Laparoscopic surgery for gastro-oesophageal reflux: beyond the learning curve.

Abstract: From September 1991 to October 1995, 320 Nissen fundoplications were undertaken laparoscopically by 12 surgeons at a single institution. To assess the performance of the procedure in the hands of five 'experienced' surgeons, the first 20 procedures performed by each surgeon or surgical trainee were excluded, providing a group of 174 patients for review. A short loose 360 degrees fundoplication was performed in all instances, with short gastric vessel division performed in 35.0 per cent of patients and hiatal repair in 66.7 per cent. Median operating time was 80 (range 30-210) min and median postoperative stay was 3 (range 1-19) days. Sixteen procedures (9.2 per cent) could not be completed laparoscopically and required conversion to open surgery. Some 144 patients were reviewed by a scientific officer 3 months after surgery, 85 at 12 months, and 32 at 2 years, using a standard clinical questionnaire. All but one were free from reflux symptoms, although 20.1 per cent reported some dysphagia at 3 months' follow-up; this figure declined to 11 per cent at 12 months and 6 per cent (two of 34 patients) at 2 years. At each follow-up interval, 91 per cent of patients were satisfied with the outcome of the surgery. Objective testing with oesophageal motility (75 patients) and barium swallow (113) studies 3-6 months after surgery confirmed the clinical outcome. Complications occurred in nine patients (5.2 per cent); four (2.3 per cent) of these required a subsequent operation within 30 days of surgery for bleeding (one patient), paraoesophageal herniation (one) and dysphagia (two). A further procedure was necessary in six other patients (3.4 per cent) for late problems, including paraoesophageal herniation (two), hiatal stenosis (three) and gastric obstruction (one). Revision was performed laparoscopically in two patients. The clinical results of laparoscopic Nissen fundoplication by 'experienced' laparoscopic surgeons were comparable with those of open surgery.

The Ratio of Messenger RNA Levels of Receptor Activator of Nuclear Factor κB Ligand to Osteoprotegerin Correlates with Bone Remodeling Indices in Normal Human Cancellous Bone but Not in Osteoarthritis

Abstract: skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor KB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA, (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.