Package inserts for prescribed medicines: what minimum information do patients need?

The information a patient needs about a prescribed medicine can be determined by considering what responsibilities he can assume in relation to taking medicine. When the medicine has been dispensed the patient needs to know how to take the drug; how to store the drug; how it is expected to help; and how to recognise problems and what to do about them. A guide was designed to specify what information is required to meet these needs. Using this guide, a set of minimum information on tetracycline was prepared that aimed at being brief, specific, and readable. The best format for the information remains to be determined. Since leaflets produced by professional organisations are generally unsuitable for these purposes, information sets should be put together by small independent groups consisting of clinical pharmacologists, clinicians, pharmacists, and consumers. Each country should produce its own sets, adapting model sets to the circumstances of local practice.     

Why do cells need an assembly machine for RNA-protein complexes?

Small nuclear ribonucleoproteins (snRNPs) are crucial for pre-mRNA processing to mRNAs. Each snRNP contains a small nuclear RNA (snRNA) and an extremely stable core of seven Sm proteins. The snRNP biogenesis pathway is complex, involving nuclear export of snRNA, Sm-core assembly in the cytoplasm and re-import of the mature snRNP. Although in vitro Sm cores assemble readily on uridine-rich RNAs, the assembly in cells is carried out by the survival of motor neurons (SMN) complex. The SMN complex stringently scrutinizes RNAs for specific features that define them as snRNAs and identifies the RNA-binding Sm proteins. We discuss how this surveillance capacity of the SMN complex might ensure assembly of Sm cores only on the correct RNAs and prevent illicit, potentially deleterious assembly of Sm cores on random RNAs.     

Why do worms need cholesterol?

Cholesterol is a structural component of animal membranes that influences fluidity, permeability and formation of lipid microdomains. It is also a precursor to signalling molecules, including mammalian steroid hormones and insect ecdysones. The nematode Caenorhabditis elegans requires too little cholesterol for it to have a major role in membrane structure. Instead, its most probable signalling functions are to control molting and induce a specialized non-feeding larval stage, although no cholesterol-derived signalling molecule has yet been identified for these or any other functions.     

Why do viruses need phloem for systemic invasion of plants?

Plant viruses use sieve elements in phloem as the route of long-distance movement and systemic infection in plants. Plants, in turn, deploy RNA silencing, R-gene mediated defence and other mechanisms to prevent phloem transport of viruses. Cell-to-cell movement of viruses from an initially infected leaf to stem and other parts of the plant could be another possibility for systemic invasion, but it is considered to be too slow. This idea is supported by observations made on viruses that are deficient in phloem loading. The leaf abscission zone forming at the base of the petiole may constitute a barrier that prevents viral cell-to-cell movement. The abscission zone and protective layer are difficult to localize in the petiole until the leaf reaches an advanced stage of senescence. Viruses tagged with the green fluorescent protein are helpful for localization and study of the developing abscission zone.     

Replication origins: why do we need so many?

During the G1 phase of the cell cycle, replication origins are prepared to fire, a process that is referred to as origin licensing. It was often pondered what a cell's fate would be if not all of its replication origins were licensed and subsequently activated during S phase. One obvious prediction was that S phase would simply be prolonged. As it turns out, however, the consequences are much more complex. A short G1 phase enforced by premature entry into S phase, or other events that negatively affect origin licensing, will ultimately compromise the cell's ability to complete DNA replication before entering mitosis. As a result, the cell becomes genomically unstable when it attempts to repair unreplicated DNA during anaphase. Thus, the density of active replication origins in the chromosomes of eukaryotic cells determines S phase dynamics and chromosome stability during mitosis.     

Why do we need quality-assured diagnostic tests for sexually transmitted infections?

The bacterial sexually transmitted infections (STIs) syphilis, gonorrhoea and chlamydia can all be cured with a single dose of antibiotic. Unfortunately, however, these infections often remain undiagnosed as many infected individuals have few if any symptoms. Diagnostic tests with high sensitivity and specificity are available for all three infections but, owing to their expense and the lack of laboratory capacity, most people in developing countries do not have access to these tests. There is a great need for simple, cheap diagnostic tests for STIs that can be performed at the point of care, enabling treatment to be given immediately. It is hoped that recent advances in our understanding of the pathogenesis of these infections, and the availability of the complete genome sequences for each causative organism, will lead to the development of improved point-of-care tests that will reduce the burden of these diseases in developing countries.     

Long term management of duodenal ulcer in general practice: How best to use cimetidine?

Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine. Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses (group 1), and the remaining third were given intermittent “healing” doses for four to eight weeks if a symptomatic recurrence was judged to have occurred (group 2). Life table analysis showed that the probability of remaining free of clinically important symptoms five years after the start of treatment was 24% (95% confidence interval (CI) 15·5% to 32·6%) in group 1 compared with nil in group 2 (p<0·0001). The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2, respectively (p<0·0001; 95% CI of the median difference 36 to 76). Over the five years 10 patients suffered major complications, two requiring emergency surgery, while a further nine had elective surgery because of the failure of medical treatment. There were no deaths that could be attributed either to ulceration or to treatment with cimetidine.Medical management was therefore very satisfactory for most patients, though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms. As 80% of patients studied relapsed during the two years after a healing course of cimetidine, continuous treatment will benefit many patients treated in general practice.     

A need for niches?

The idea that different species must have distinct ecologies if they are to coexist has been challenged recently by the claim that some models involving stochastic factors or clumped spatial distributions permit stable coexistence of species that are identical or differ only in competitive ability. However, these models have been misinterpreted; except in rather limited circumstances, they provide further support for the notion that species must be sufficiently ecologically distinct to coexist stably. The possible, limited, exceptions to this rule involve social factors by which individuals of a species discriminate between heterospecifics and conspecifics without there being any true ecological differences between species.     

Introduction: why do we need a science of well-being?

Introduction: why do we need a science of well-being?     

Ultrastructure in cell biology: do we still need it?

John Heuser is being honored in this special issue for his enormous contributions to cell biology using morphological approaches. Foremost in this context is his ability to use light and electron microscopy to visualize structures and processes such that the information has both scientific and artistic value. The beauty of his images helps to focus the observer more intensely on the scientific messages, which have been numerous and important. His recent studies of living cells using state-of-the-art light and video microscopy fits into a general pattern of a huge explosion in the application of these methods worldwide that is revolutionizing cell biology. However, whereas John Heuser continues to use light microscopy (LM) for a low-resolution global and dynamical overview he then moves on to the electron microscopy (EM) level to see the details; in this he is--unfortunately--in a minority; and EM is an approach that a majority of today's cell biologists never use. The continued drop in EM usage has already been articulated in recent reviews. Here, I suggest that an additional problem for EM in cell biology, in its continued crises, is the declining number of scientists who can confidently interpret the--admittedly--complex information in most electron micrographs of cells. A major re-education is needed, or cell biology as a discipline will have a real problem in the 21st century.     

D-2 dopamine autoreceptor selective drugs: do they really exist?

The catecholamine dopamine plays an important role as a neurotransmitter or neurohormone in the brain and pituitary gland. Dopamine exerts its effects through activation of two types of receptors called D-1 and D-2. These receptors are distinguished by their different pharmacological characteristics and signal transduction mechanism(s). Release of dopamine inhibits the activity of dopaminergic neurons through activation of so-called dopamine autoreceptors which are of the D-2 type. In general, these receptors occur both in the soma-dendritic region of the dopaminergic neuron, where they are involved in the inhibition of the firing rate and on the dopaminergic terminals where they mediate the inhibition of dopamine synthesis and release. D-2 receptors occur also on the target cells of dopaminergic neurons both in the brain (postsynaptic D-2 receptors) and pituitary gland. On the basis of data gathered from in vivo (behavioral- as well as electrophysiological) studies it has been concluded that D-2 agonists are much more potent at dopamine autoreceptors as compared to postsynaptic D-2 receptors, indicating the possibility of a pharmacological distinction between these differentially located D-2 receptors. This concept led to the introduction of a whole group of drugs allegedly displaying a selective agonist profile at the dopamine autoreceptor. In contrast, biochemical (in vitro) studies with brain tissue as well as the pituitary gland, did not reveal any significant difference between the pharmacological profiles of autoreceptors and postsynaptic D-2 receptors. In the present minireview a balanced discussion is presented of these in vivo and in vitro findings and it is concluded that both autoreceptors as well as postsynaptic D-2 receptors are similar if not identical entities.