Effect of an educational intervention on requesting behaviour by a medical admission unit.

BACKGROUND: Previous studies have shown that of all the tests requested of hospital laboratories, 25-40% are thought to be unnecessary. Our hospital laboratory observed that a significant number of requests from the medical admissions unit (MAU) were probably inappropriate. In an attempt to improve requesting behaviour this observation was investigated and an educational intervention employed. METHODS: We performed a survey of requesting behaviour by the MAU and a local protocol was designed as an audit standard. The influence of the educational intervention on requesting behaviour was audited. RESULTS: The generation of local guidelines and an educational intervention to promote them, significantly changed requesting behaviour. The main effect was the reduction in requesting of thyroid function tests, lipid profiles and coagulation screens. CONCLUSIONS: This process highlighted inappropriate requesting behaviour from the MAU which, following a process of investigation and education, resulted in a significant change with an associated cost benefit.

Defining the role of lipoprotein apheresis in the management of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder characterized by a marked elevation of serum low-density lipoprotein (LDL) cholesterol (LDL-C) concentration, which in turn is associated with a greatly increased risk of premature cardiovascular disease. International consensus recommends the use of statins as the first line of treatment for patients with this condition. However, homozygote FH patients with persistently elevated LDL-C levels are usually resistant to multiple-drug therapy. Fortunately, LDL apheresis (or simply 'lipoprotein apheresis') provides a treatment option for patients who are refractory or intolerant to lipid-lowering medications, or if there is progressive cardiovascular disease despite maximal drug therapy. Lipoprotein apheresis is an extracorporeal LDL-C-lowering treatment similar in concept to renal dialysis. There are now five main methods for extracorporeal lipoprotein apheresis in use, namely dextran sulfate adsorption (DSA), heparin extracorporeal LDL precipitation (HELP), polyacrylate full blood adsorption (PFBA or DALI® system) using hemoperfusion, immunoadsorption, and filtration plasmapheresis. Lipoprotein apheresis has been shown to be successful in reducing LDL-C levels, as well as levels of lipoprotein(a) [Lp(a)], a prothrombotic proatherogenic lipoprotein. In contrast, however, lipoprotein apheresis seems to have a smaller effect in preventing atherosclerosis progression, thus suggesting that a major component of the reduction in cardiovascular events may be mediated by mitigating Lp(a) levels. Side effects are infrequent and mild, and have mainly consisted of lightheadedness, nausea, vomiting, and hypotension. As these are often bradykinin-mediated and associated with concomitant ACE inhibitor use, angiotensin type 2 receptor antagonists should be used instead of ACE inhibitors with DALI and PFBA. Nevertheless, there is scope for wider application of lipoprotein apheresis. The high cost and invasive nature of lipoprotein apheresis limits uptake; however, it is an important treatment modality that should be considered in carefully selected patients. National and international registries compiling outcome data for lipoprotein apheresis need to be established to help expand the evidence base regarding its effectiveness.

Integrating provision of specialist lipid services with cascade testing for familial hypercholesterolaemia.

PURPOSE OF REVIEW: To highlight the unmet need for identifying individuals with familial hypercholesterolaemia and exploring the implications that this will have for local and national healthcare services. RECENT FINDINGS: A pathway utilising DNA testing for the diagnosis of familial hypercholesterolaemia, and subsequent cascade testing has been developed in Wales. SUMMARY: Undiagnosed familial hypercholesterolaemia carries a high risk of cardiovascular disease, which is easily preventable with pharmacotherapy, if individuals are appropriately diagnosed, and affected family members identified. The use of DNA testing is cost-effective and allows for efficient cascade testing. This has implications for local services and highlights unmet educational and clinical requirements in clinical lipidology.

NO metabolite flux across the human coronary circulation.

OBJECTIVES: The theory of a red blood cell derived nitric oxide (NO) reserve conserving NO bioactivity and delivering NO as a function of oxygen demand has been the subject of much interest. We identified the human coronary circulation as an ideal model system in which to analyse NO metabolites because of its large physiological oxygen gradient. Our objective was to identify whether oxygen drove apportion between various NO metabolite species across a single vascular bed. METHODS: Plasma and red blood cell NO metabolites were assessed from the left main coronary artery, coronary sinus and pulmonary artery (providing cross heart and cross pulmonary analysis) of healthy subjects under resting conditions and following administration of an inhibitor of NO biosynthesis. Physiological parameters and angiographic data were monitored throughout the study. RESULTS: Under baseline conditions we observed significant metabolite flux upon the transit of blood across the coronary and pulmonary vascular beds. Whilst there was no net loss of NO through the coronary circulation (p=0.0759), plasma nitrite/protein NO (excluding nitrate) (p=0.0279) and red blood cell sulphanilamide labile signal (p=0.0143) decreased whereas haemoglobin-bound NO increased three-fold (p=0.005). These changes across the coronary circulation were reversed through the pulmonary circuit with red blood cell sulphanilamide labile signal (p=0.0143) and plasma nitrite/protein NO (p=0.0279) increasing and haemoglobin-bound NO decreasing. Blockade of NO synthesis increased mean arterial blood pressure (p<0.01) and reduced coronary artery diameter (p<0.05), however we observed similar apportion of NO metabolites across the heart and lung with no net loss or gain in total NO metabolites. CONCLUSIONS: For the first time in human subjects across the resting coronary circulation we reveal significant re-apportionment of NO between metabolite species which correlate with haemoglobin oxygen saturation. These changes occur even within the transit time of blood across this single vascular bed. We demonstrate no net loss/gain of NO from the total metabolite pool across the coronary circulation even where NO biosynthesis is inhibited.

Red blood cell nitric oxide as an endocrine vasoregulator: a potential role in congestive heart failure.

BACKGROUND: A respiratory cycle for nitric oxide (NO) would involve the formation of vasoactive metabolites between NO and hemoglobin during pulmonary oxygenation. We investigated the role of these metabolites in hypoxic tissue in vitro and in vivo in healthy subjects and patients with congestive heart failure (CHF). METHODS AND RESULTS: We investigated the capacity for red blood cells (RBCs) to dilate preconstricted aortic rings under various O2 tensions. RBCs induced cyclic guanylyl monophosphate-dependent vasorelaxation during hypoxia (35+/-4% at 1% O2, 4.7+/-1.6% at 95% O2; P<0.05). RBC-induced relaxations during hypoxia correlated with S-nitrosohemoglobin (SNO-Hb) (R2=0.88) but not iron nitrosylhemoglobin (HbFeNO) content. Relaxation responses for RBCs were compared with S-nitrosoglutathione across a range of O2 tensions. The fold increases in relaxation evoked by RBCs were significantly greater at 1% and 2% O2 compared with relaxations induced at 95% (P<0.05), consistent with an allosteric mechanism of hypoxic vasodilation. We also measured transpulmonary gradients of NO metabolites in healthy control subjects and in patients with CHF. In CHF patients but not control subjects, levels of SNO-Hb increase from 0.00293+/-0.00089 to 0.00585+/-0.00137 mol NO/mol hemoglobin tetramer (P=0.005), whereas HbFeNO decreases from 0.00361+/-0.00109 to 0.00081+/-0.00040 mol NO/mol hemoglobin tetramer (P=0.03) as hemoglobin is oxygenated in the pulmonary circulation. These metabolite gradients correlated with the hemoglobin O2 saturation gradient (P<0.05) and inversely with cardiac index (P<0.05) for both CHF patients and control subjects. CONCLUSIONS: We confirm that RBC-bound NO mediates hypoxic vasodilation in vitro. Transpulmonary gradients of hemoglobin-bound NO are evident in CHF patients and are inversely dependent on cardiac index. Hemoglobin may transport and release NO bioactivity to areas of tissue hypoxia or during increased peripheral oxygen extraction via an allosteric mechanism.