From cardiac repair to cardiac regeneration--ready to translate?

Cardiovascular disease is a major public health challenge in the western world. Mortality of acute events has improved, but more patients develop HF--a condition affecting up to 22 million people worldwide. Cell transplantation is the first therapy to attempt replacement of lost cardiomyocytes and vasculature to restore lost contractile function. Since the first reported functional repair after injection of autologous skeletal myoblasts into the injured heart in 1998, a variety of cell types have been proposed for transplantation in different stages of cardiovascular disease. Fifteen years of preclinical research and the rapid move into clinical studies have left us with promising results and a better understanding of cells as a potential clinical tool. Cell-based cardiac repair has been the first step, but cardiac regeneration remains the more ambitious goal. Promising new cell types and the rapidly evolving concept of adult stem and progenitor cell fate may enable us to move towards regenerating viable and functional myocardium. Meeting a multidisciplinary consensus will be required to translate these findings into safe and applicable clinical tools.     

Renal-dose dopamine: from hypothesis to paradigm to dogma to myth and, finally, superstition?

Acute renal failure (ARF) is common in the critically ill and is associated with a high mortality rate. Its pathogenesis is not understood. Because animal models use ischemia to induce experimental ARF, there is the widespread belief that lack of blood flow is responsible for ARF. Low-dose dopamine (LDD) has been shown to increase renal blood flow in animal and in human volunteers. Thus, it has been administered to humans for almost 3 decades in the belief that it would lead to renal arterial vasodilation and increase renal blood flow (RBF). However, the etiology of ARF in critical illness is likely multifactorial, and the contribution of hypovolemia and reduced renal perfusion is unknown. Furthermore, interindividual variation in the pharmacokinetics of dopamine typically results in poor correlation between blood levels and administered dose, making accurate and reliable delivery of LDD difficult. Finally, dopamine is a proximal tubular diuretic that increases Na(+) delivery to tubular cells, thus increasing their oxygen demands. Accordingly, even if LDD were able to preferentially increase RBF, there is no guarantee that it would restore renal parenchymal oxygen homeostasis. More important, 2 meta-analyses and a large double-blind, prospective, multiple-center, randomized controlled trial have failed to demonstrate that dopamine protects the kidney in critically ill patients with ARF. Currently, there is insufficient evidence to support the use of renal-dose dopamine in the intensive care unit.     

Who is best qualified to teach bioscience to nurses?

Since the professions moved into higher education, diversity has developed in the amount, depth and method of bioscience teaching in nursing and midwifery courses. Bioscience encompasses biology, life science, anatomy and physiology. This diversity is a cause for concern at a time when nurses and midwives are taking on more of the traditional medical tasks such as prescribing and running clinics. Students need to acquire a sound grasp of anatomy and physiology and to achieve this a substantial amount of curriculum time needs to be devoted to bioscience. The main argument concerns not what should be taught but who should teach bioscience to students; whether this should be specialist lecturers from higher education science departments or nursing and midwifery teachers from health studies. This article makes the case for collaboration involving subject specialists and nursing/midwifery teachers and this is illustrated by examples of how such collaboration works in one higher education institution to produce a practical laboratory-based course. The conclusion is that time spent in life science laboratories should not be considered a waste of nursing/midwifery teaching time because the life science laboratory is a microcosm of clinical practice. This relevance can be emphasised through collaboration between nursing and bioscience lecturers.     

Treatment strategies for multiple sclerosis: When to start,when to change,when to stop?

Multiple sclerosis(MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.