The Achilles heel of BCG

There have been multiple explanations put forward to try to explain the variable efficacy of the BCG vaccine. Here I propose the new hypothesis that the primary flaw of BCG is its inability to effectively establish a population of central memory T cells. Instead, the vaccine establishes immunity represented by effector memory T cells; these distribute in the lungs and may protect humans for 10–15 years but are gradually lost. With no central memory response to compensate, the individual loses any further resistance to tuberculosis. This may have serious implications for vaccine design, given the emphasis on developing recombinant forms of BCG.     

Hepatitis C recurrence: the Achilles heel of liver transplantation

Hepatitis C virus (HCV) infection is the most common indication for liver transplantation worldwide; however, recurrence post transplant is almost universal and follows an accelerated course. Around 30% of patients develop aggressive HCV recurrence, leading to rapid fibrosis progression (RFP) and culminating in liver failure and either death or retransplantation. Despite many advances in our knowledge of clinical risks for HCV RFP, we are still unable to accurately predict those most at risk of adverse outcomes, and no clear consensus exists on the best approach to management. This review presents a critical overview of clinical factors shown to influence the course of HCV recurrence post transplant, with particular focus on recent data identifying the important role of metabolic factors, such as insulin resistance, in HCV recurrence. Emerging data for genetic markers of HCV recurrence and their usefulness for predicting adverse outcomes will also be explored.     

Pulmonary vein stenosis: still the Achilles heel of ablation for atrial fibrillation?

Atrial fibrillation (AF) can be eliminated by (i) targeted deliveryto focal ‘sites’ within the pulmonary vein (PV),by (ii) PV isolation through circumferential or segmental ablationat the venoatrial junction, or by (iii) electrical isolationfrom the left atrium (LA) outside the PV ostia. PV stenosisdevelops in 1–10% of patients undergoing ablation. Sofar, the clinical presentation, investigation, management, andoutcome of this disease have been incompletely reported. Understanding PV anatomy is crucial both for PV ablation andfor prevention of PV stenosis. Using magnetic resonance (MR)scanning, Cato et al.¹ have reported that 38% of patientsexhibit a variant anatomy (short or long common left trunk,right middle or right upper PV). In addition, very close proximitybetween the ostia of the right and the left PVs was observed.The diameters of the four regular PVs did not differ significantly,but PV and LA seemed larger     

Targeting the glycans of gp120: a novel approach aimed at the Achilles heel of HIV

The development of drug resistance in HIV compromises the long-term efficacy of current therapies. Furthermore, vaccine development faces huge problems, mainly because of the low antigenicity and immunogenicity of the HIV envelope glycoprotein gp120 and the efficient hiding of highly immunogenic epitopes by its glycans. There is evidence that mutant HIV strains containing glycosylation site deletions trigger the production of specific neutralising antibodies to previously hidden gp120 epitopes. I present a hypothesis that development of resistance against drugs that target the glycans on gp120 would result in a marked enhancement of neutralisation of HIV by the immune system--ie, drugs directed against the carbohydrate component of gp120 will select for mutant virus strains that progressively gain deletions in the glycosylation sites of gp120. Previously hidden epitopes would then be uncovered, and the virus will become highly susceptible to markedly increased immunological neutralisation. I believe this novel approach may become an entirely new therapeutic concept that exploits the high mutation rate of HIV and allows drug therapy to act in concert with a triggered immune response to suppress HIV more efficiently. Moreover, this approach could be applied to treat other chronic infections by viruses that contain a glycosylated envelope (eg, hepatitis B and C).     

The achilles heel in melatonin: asthma

Asthma is a clinical syndrome characterized by chronic airway inflammation, airway responsiveness, and expiratory airflow limitation. Nocturnal symptoms and decreases in lung function are common aspects of the asthma clinical syndrome. Nocturnal symptoms also appear to be associated with asthma-related mortality. In addition to its importance to the regulation of human circadian rhythms, an accumulating body of evidence also suggests that melatonin is also involved in the regulation of smooth muscle tone. For this reason, this study aimed to evaluate contraction and relaxation responses in tracheal smooth muscle rings obtained from rats treated with melatonin. Following administration of melatonin (50mg/kg/day) at the same time every day for 6 weeks, in vitro organ bath experiments were performed with rat tracheal preparations exposed to contractile (acetycholine and serotonin) and relaxant (theophylline and papaverine) agents. Melatonin treatment strengthened contraction responses, but did not affect relaxation responses in rat tracheal preparations. We think that melatonin might play a role in the pathogenesis of nocturnal asthma. Therefore, clinicians should be aware of the importance of melatonin to nocturnal exacerbation of asthma symptoms and alert asthmatic patients that use exogenous melatonin supplementation of its potential negative effects.     

The effect of heel elevation in Parkinsonian gait

The effect of heel elevation of shoes in Parkinson's disease was analyzed by using two gait measurement systems. The heel elevation brought about some improvement of walking in the patients with Parkinson's disease with shortening of a stride period, a step period and the transition time of the plantar pressure peak from heel contact to toe off. After measurement study of the gait, all the patients answered the best heel height of shoes was higher than that of their casual footwear or the same. This simple treatment method may be also effective for fall prevention in patients with Parkinson's disease, and further investigation with follow-up observations should be necessary to verify the effect.