Malaria vaccines: where are we and where are we going?

Malaria is still killing over one million people each year and its incidence is increasing. The need for an effective vaccine is greater than ever. A major difficulty with vaccine research is that the malaria parasite presents thousands of antigens to the human immune system that vary throughout its life cycle. Identifying those that may prove to be vaccine targets is complicated and time consuming. Most vaccines are targeted at individual stages of the malaria life cycle, although it is likely that only the development of a multistage vaccine will offer complete protection to both visitors to, and residents of, a malaria-endemic area. With the development of a successful vaccine other issues such as cost, distribution, education, and compliance will have to be addressed. This review describes some of the current vaccine candidates for immunising against malaria.     

How clonal are bacteria?

Data from multilocus enzyme electrophoresis of bacterial populations were analyzed using a statistical test designed to detect associations between genes at different loci. Some species (e.g., Salmonella) were found to be clonal at all levels of analysis. At the other extreme, Neisseria gonorrhoeae is panmictic, with random association between loci. Two intermediate types of population structure were also found. Neisseria meningitidis displays what we have called an "epidemic" structure. There is significant association between loci, but this arises only because of the recent, explosive, increase in particular electrophoretic types; when this effect is eliminated the population is found to be effectively panmictic. In contrast, linkage disequilibrium in a population of Rhizobium meliloti exists because the sample consisted of two genetically isolated divisions, often fixed for different alleles: within each division association between loci was almost random. The method of analysis is appropriate whenever there is doubt about the extent of genetic recombination between members of a population. To illustrate this we analyzed data on protozoan parasites and again found panmictic, epidemic, and clonal population structures.     

Why are angles misperceived?

Although it has long been apparent that observers tend to overestimate the magnitude of acute angles and underestimate obtuse ones, there is no consensus about why such distortions are seen. Geometrical modeling combined with psychophysical testing of human subjects indicates that these misperceptions are the result of an empirical strategy that resolves the inherent ambiguity of angular stimuli by generating percepts of the past significance of the stimulus rather than the geometry of its retinal projection.     

What are the predictors of post-ERCP pancreatitis,and how useful are they?

Acute pancreatitis is one of the major complications of ERCP. It is of paramount importance that we accurately identify which patients will go on to develop post-ERCP pancreatitis. As most ERCPs are performed on an outpatient basis, early evaluation can allow safe discharge of the majority of patients who will not develop post-ERCP pancreatitis or develop only mild symptoms that will be self-limited. Alternatively, early detection of those patients who will go on to develop moderate or severe post-ERCP pancreatitis can guide decisions regarding hospital admission and aggressive management and can help direct the use of targeted therapies that have the potential to prevent or mitigate pancreatic inflammation. Thus, significant efforts have focused on trying to identify predictors of post-ERCP pancreatitis. These parameters can be organized into three categories of tests: 1) pancreatic enzymes as markers of pancreatic injury: serum amylase/urine amylase; 2) markers of proteolytic activation: trypsinogen, trypsinogen activation peptide; 3) markers of systemic inflammation: C-reactive protein, various interleukins such as IL-6 and IL-10. A serum amylase level greater than 4-5 times the upper reference limit in conjunction with clinical symptoms has been shown to be an accurate and reliable predictor of post-ERCP pancreatitis. However, the exact timing and level of amylase elevation remains debatable. Urine testing of amylase and trypsinogen-2 in post-ERCP patients has also been shown to be highly sensitive and specific for detecting pancreatitis. The main advantage of these urinary markers is that they are available as rapid dipstick tests. Serum trypsinogen-2 levels have also been studied in post-ERCP pancreatitis patients; high levels seem to correlate with severity of disease. Among the markers of systemic inflammation, serum CRP is an accurate and readily available laboratory test for predicting severity of post-ERCP pancreatitis, but it appears to be helpful at 24-48 hours and, therefore, is not an early marker. Several other markers remain investigational and have not yet found wide clinical applicability.     

Children outgrowing asthma: What are the odds,what are the facts?

It's every parent's hope, but can children who have asthma really outgrow it by the time they become adults?     

Interventional cardiology. Where are we and where are we going from here?

This article summarizes 20 years of percutaneous interventional cardiology for coronary angioplasty. During this period, interventional cardiology has evolved faster than any other type of treatment in the field of cardiovascular diseases. We describe the early results of interventional cardiology, the increase in primary success rates and the reduction in complication rates for percutaneous techniques during this period, which coincided with the introduction of technological advances. In the early 1990s, primary success rates for the treatment of coronary lesions stood at 86%-88%, with a restenosis rate of 30%-40% at 6-month follow-up. Current primary success rates have risen to over 95% with a restenosis rate of under 10%, even for many types of lesions classically considered complex. Currently the main limitations in interventional cardiology remain coronary segments that cannot be accessed due to chronic total occlusion, or severe proximal tortuosity or calcification. Rapid improvements have led to broader clinical indications for percutaneous revascularization procedures, and have made frequent updates of clinical practice guidelines necessary. Meanwhile, comparative studies involving other modes of surgical revascularization have become extremely difficult because percutaneous methods used in long-term studies begun 5 to 10 years have become obsolete.     

Probiotics: what are they? What are their effects on gut physiology?

Probiotics can be defined as microbial cells that have a beneficial effect on the health and well-being of the host. Since the gastrointestinal mucosa is the surface of contact with probiotics, it seems evident that the first effects of probiotics relate to digestive function. A brief review of the literature indicates that probiotics have very few effects on the main physiological functions of the gastrointestinal tract, which are digestion, absorption and propulsion. The main action of probiotics can be summarised as a reinforcement of the intestinal mucosal barrier against deleterious agents. Experimental data indicate that some probiotics reduce pathological alterations in paracellular permeability to large molecules or bacteria, stimulate mucosal immunity, display a trophic action on the mucosa, reduce mucus degradation and interact with mediators of inflammation. Yoghurt may help lactose digestion, and some data needing confirmation indicate a stimulation of water absorption and an acceleration of intestinal transit by some bacteria.     

To whom are we answerable?

In comments stimulated by Erica Bates' book Health System and Public Scrutiny: Australia, Britain, and the United States (New York: St. Martin's; 1983), the author discusses medicine's lack of responsiveness to criticism from patients and peers. Lay critics focus on observable medical behavior and seldom delve into the "heart of medicine," the clinical consultation. Because of centuries of an overcrowded market, the consultation has been designed to "mystify rather than educate, to disguise spontaneous improvement as the effect of treatment, and iatrogenic illness as the effect of disease." Before 1935 medicine was cheap and relatively harmless; however, now it is expensive and potentially destructive and therefore demands discriminate use. Unfortunately, the retention of brief consultations hinders accountability. If practitioners were answerable to their patients, a beginning could be made toward satisfying a demand for public scrutiny.     

Death certificate completion: how well are physicians trained and are cardiovascular causes overstated?

PURPOSE: To determine the ability of residents in completing death certificates correctly. METHODS: A total of 4800 residents were asked to complete a survey and cause-of-death statement using a sample case of in-hospital death due to urosepsis, of whom 590 residents (12%) responded. A scoring scale designed based on instructions from the National Association of Medical Examiners and the American College of Pathologists was used to measure responses quantitatively. RESULTS: Overall performance was poor, with only 23% (n = 137) of responses in the optimal scoring range. The average score was influenced significantly by level of residency training, as well as previous experience, prior formal training, and awareness of the guidelines regarding death certificate completion. Optimal scores correlated with level of residency training and prior formal training in death certificate completion, suggesting the benefits of experience and instruction. Forty-five percent (n = 267) of respondents incorrectly identified a cardiovascular event as the primary cause of death. CONCLUSION: The residents in this study demonstrated suboptimal performance in death certificate completion. Cardiovascular events were often incorrectly identified as the primary cause of death. Formal training can improve performance and should be emphasized in medical schools and residencies.