The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Surgery for primary hyperparathyroidism performed under local anaesthesia

Patients with primary hyperparathyroidism are often elderly with cardiovascular disease and in some an operation might be hazardous owing to anaesthetic complications. A technique for operation for primary hyperparathyroidism under local anaesthesia is described. The method uses a unilateral approach. Seventeen consecutive patients operated on under local anaesthesia were compared with a group of 15 patients undergoing surgery under general anaesthesia. Normocalcaemia was achieved in 14 patients in each group. There was no difference in the extent of pain or the overall well-being between the two groups as determined by a visual analogue scale. Patients receiving local anaesthesia, however, experienced significantly less nausea after operation (P < 0.01). There was more fluctuation in blood pressure and heart rate in the general anaesthesia group compared with the other group. Surgery for primary hyperparathyroidism can be performed safely under local anaesthesia, and could be offered to patients if general anaesthesia were not suitable or involved an increased perioperative risk. It should not be recommended for routine use in patients who are fit for general anaesthesia

Autonomic dysfunction in Alzheimer's disease

Twenty-nine patients fitting the NINCDS-ADRDA criteria of Alzheimer's disease participated in a study of autonomic functions. A number of tests on parasympathetic and sympathetic functions were made. Eighteen of the patients were tested a second time one year later. Fifteen healthy subjects with no family history of dementia disorders served as controls. Compared to the controls, the patients showed signs suggesting autonomic dysfunction affecting parasympathetic, as well as vasomotor sympathetic, functions

Acute right ventricular failure-from pathophysiology to new treatments

The right ventricle (RV) provides sustained low-pressure perfusion of the pulmonary vasculature, but is sensitive to changes in loading conditions and intrinsic contractility. Factors that affect right ventricular preload, afterload or left ventricular function can adversely influence the functioning of the RV, causing ischaemia and right ventricular failure (RVF). As RVF progresses, a pronounced tricuspid regurgitation further decreases cardiac output and worsens organ congestion. This can degenerate into an irreversible vicious cycle. The effective diagnosis of RVF is optimally performed by a combination of techniques including echocardiography and catheterisation, which can also be used to monitor treatment efficacy. Treatment of RVF focuses on alleviating congestion, improving right ventricular contractility and right coronary artery perfusion and reducing right ventricular afterload. As part of the treatment, inhaled nitric oxide or prostacyclin effectively reduces afterload by vasodilating the pulmonary vasculature. Traditional positive inotropic drugs enhance contractility by increasing the intracellular calcium concentration and oxygen consumption of cardiac myocytes, while vasopressors such as norepinephrine increase arterial blood pressure, which improves cardiac perfusion but increases afterload. A new treatment, the calcium sensitiser, levosimendan, increases cardiac contractility without increasing myocardial oxygen demand, while preserving myocardial relaxation. Furthermore, it increases coronary perfusion and decreases afterload. Conversely, traditional treatments of circulatory failure, such as mechanical ventilation and volume loading, could be harmful in the case of RVF. This review outlines the pathophysiology, diagnosis and treatment of RVF, illustrated with clinical case studies

Side localization of parathyroid adenomas by simplified intraoperative venous sampling for parathyroid hormone

Side localization of parathyroid adenomas was performed by venous sampling for intact parathyroid hormone (PTH) in 20 consecutive patients with primary hyperparathyroidism (pHPT) after induction of anesthesia. The results were thus available during surgery. Nineteen of the patients had solitary parathyroid adenoma, and one had hyperplasia. There was no complication to the procedure. A lateralizing PTH gradient for a parathyroid adenoma was obtained in 13 patients. At surgery 12 of them (92%) were proved correct; that is, the adenoma was localized on the same side. Thus the technique correctly lateralized the adenoma in 12 of 19 patients (63%). We therefore conclude that the method of intraoperative venous sampling for intact PTH is safe, and the predictive value of a lateralizing gradient is high. It could therefore be used as an adjunct to surgical skill and noninvasive localization procedures in selected cases, for instance in patients with prior neck surgery and hypercalcemic crisis