Can lipofuscin accumulation be prevented?

During normal autophagic degradation of mitochondria and iron-containing proteins in lysosomes, iron is released intralysosomally where it may react with hydrogen peroxide forming hydroxyl radicals (Fenton reaction). Depending on their rate of formation, these highly reactive radicals can cross-link intralysosomal material, leading to lipofuscin formation, or destabilize the lysosomal membrane, which induces apoptosis/necrosis. Since the sensitivity of lysosomes to oxidative stress can be manipulated by altering the intralysosomal level of redox-active iron, it follows that lipofuscin formation might also be influenced. It is suggested that pulse doses of iron chelators that easily penetrate membranes could be used to diminish lipofuscinogenesis.     

Can diabetic neuropathy be prevented?

The incidence of diabetes and its complication have rapidly increased. Decreased quality of life and increased mortality are the major problems of people with diabetes. These problems are mainly caused by chronic complications. The incidence of diabetic neuropathy, which is one of these chronic complications, approaches 50% in most diabetic patients. The intensive metabolic management alone cannot completely prevent the development and progression of diabetic complications. Therefore, blocking and management of pathogenic mechanism of complication are required. Pathogenesis of diabetic neuropathy has multifactorial causes. Diabetic neuropathy is thought to occur both from direct hyperglycemia-induced damage to the nerve parenchyma and from neuronal ischemia brought about indirectly by hyperglycemia-induced decreases in neurovascular flow. The effects of hyperglycemia get converted to neuronal dysfunction via at least three secondary biochemical pathways: the polyol pathway, non-enzymatic glycation of proteins, oxidative stress and protein kinase C, and the interactions between them. Because of these interactions, interference with one of these biochemical pathways could either worsen or attenuate the effects of the others. So, the use of therapeutic intervention of these pathways is inevitable and valid to prevent the progression of diabetic neuropathy. As yet, a satisfactory and fundamental, preventive, and therapeutic method is not available with us to prevent progression. So, we will introduce the earlier diagnostic methods of diabetic neuropathy and will discuss the advantages and limitations of each method.     

Can rheumatoid arthritis be prevented?

The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior to the onset of clinically apparent RA raises hopes that individuals who are at risk of future RA can be identified in a preclinical phase of disease that is defined as abnormalities of RA-related immune activity prior to the clinically apparent onset of joint disease. Additionally, there is a growing understanding of the immunologic processes that are occurring in preclinical RA, as well as a growing understanding of risk factors that may be mechanistically related to RA development. Furthermore, there are data supporting that treatment of early RA can lead to drug-free remission. Taken as a whole, these findings suggest that it may be possible to use biomarkers and other factors to accurately identify the likelihood and timing of onset of future RA, and then intervene with immunomodulatory therapies and/or risk factor modification to prevent the future onset of RA in at-risk individuals. Importantly, several clinical prevention trials for RA have already been tried, and one is underway. However, while our growing understanding of the mechanisms and natural history of RA development may be leading us to the implementation of prevention strategies for RA, there are still several challenges to be met. These include developing sufficiently accurate methods of predicting those at high risk of future RA so that clinical trials can be developed based on accurate rates of development of arthritis and subjects can be adequately informed of their risk of disease, identifying the appropriate interventions and biologic targets for optimal prevention, and addressing the psychosocial and economic aspects that are crucial to developing broadly applicable prevention measures for RA. These issues notwithstanding, prevention of RA may be within reach in the near future.     

Prevention of calcific aortic stenosis by statins: myth or reality?

Degenerative calcific aortic stenosis is the most common valvular disease in the industrialised world. During the last decade, experimental studies have improved our understanding of the physiopathology of this disease. The latest data concerns the demonstration of the mode of installation and progression which resembles that of athrosclerosis. Lipid abnormalities, especially hypercholesterolaemia, are important in the initiation of the valvular lesions and also in the calcification of the aortic orifice. Experimental data and retrospective clinical studies suggest, but without proof, that statins could slow th progression of the aortic stenosis. However, the first prospective trial, recently published, questions this hypothesis. Randomised multicenter trials are currently under way and should provide the answer to the role of stetins in the prevention of aortic stenosis.     

Can severity of aortic stenosis be determined despite absent contractile reserve in low‐flow low‐gradient aortic stenosis?

A 79‐year‐old man presented with increasing breathlessness and his echocardiogram revealed severe left ventricular systolic dysfunction and low‐flow low‐gradient aortic stenosis. Low‐dose dobutamine stress echocardiography revealed the absence of contractile reserve (increase of stroke volume by ≥20% did not occur). The test would have therefore been inconclusive. However, the attainment of normal flow (FR≥200 mL/s) during dobutamine stress enabled the diagnosis of true severe aortic stenosis.     

Aortic valve replacement for aortic stenosis after previous coronary artery bypass grafting: could early reoperation be prevented?

BACKGROUND AND AIM OF THE STUDY: The study aim was to examine, retrospectively, the risk of accelerated progression of aortic stenosis (AS) and outcome after aortic valve replacement (AVR) in patients who had undergone previous coronary artery bypass graft (CABG) surgery. METHODS: Between 1994 and 2004, 81 patients with mild-to-moderate AS at the time of CABG underwent subsequent AVR. The mean EuroScore was 10.8 +/- 1.8. The population was divided into three subgroups according to the time interval between AVR and CABG: group A, < 5 years (n = 23); group B, 5-10 years (n = 34); and group C, > 10 years (n = 24). RESULTS: Mean age at the time of CABG was 70 +/- 5, 64 +/- 6 and 58 +/- 5 years in groups A, B, and C, respectively. The peak transvalvular gradient was < or = 30 mmHg in 65 patients (80.2%), and 30-50 mmHg in 16 (19.7%). Operative mortality after AVR was 16% in the overall population (30%, 11.7%, and 8.6% in groups A, B, and C, respectively). The mean time interval between CABG and AVR was 8.9 +/- 5.2 years. By multivariate analysis, a peak transvalvular gradient > or = 30 mmHg (p = 0.003), moderate calcifications with moderately-to-severely limited valve motion (p = 0.05), and left ventricular hypertrophy (LVH) (p = 0.005) were independent predictors of AVR within five years of CABG surgery. Systemic vascular atherosclerotic disease was a predictor of rapid disease progression by univariate analysis, and a predictor of operative mortality by multivariate analysis. CONCLUSION: Because of the high mortality associated with repeat operations within five years, AVR should be considered at the time of CABG in patients aged < or = 75 years, with a peak transvalvular gradient > 30 mmHg, moderately prominent calcifications with moderately to severely limited valve motion, and LVH.     

Can gastric cancer be prevented by Helicobacter pylori eradication?

Helicobacter pylori infection always causes chronic gastritis and triggers several gastroduodenal pathologies ranging from peptic ulcer disease to gastric cancer. It is well established that H. pylori eradication decreases the incidence of gastroduodenal ulcer and its recurrence. However, despite being accepted as the critical risk factor for gastric cancer, there is no conclusive evidence that H. pylori eradication decreases the incidence of gastric cancer. Bacterial virulence characteristics, as well as genetic predisposition of the host in conjunction with certain environmental conditions, are the major factors which influence the development of gastric cancer. Preclinical and clinical data suggest that reversibility of precancerous lesions (atrophic gastritis and intestinal metaplasia) is possible in some patients after H. pylori eradication. Since neoplastic lesions do not progress - or even regress in some cases - after H. pylori eradication, eradication therapy should be considered even in patients with precancerous lesions. Nonetheless, progression of atrophic gastritis and intestinal metaplasia into cancer has been also demonstrated in patients after H. pylori eradication, suggesting that there might be a point of no return where genetic changes have already happened and are irreversible despite elimination of the triggering carcinogen (H. pylori). At the present time the clinical decision to treat a patient is based on established risk profiles. A general screen-and-treat policy, although desirable, currently awaits a less complex treatment regimen.     

Can the degree of renal artery stenosis be automatically quantified?

The objective of the reported study is to validate a computer system, QUASAR, dedicated to the quantification of renal artery stenoses. This system estimates automatically the reference diameter and calculates the minimum diameter to compute a degree of stenosis. A hundred and eighty images of atheromatous stenoses between 10% and 80% were collected from two French independent protocols. For the 49 images of the EMMA protocol, the results from QUASAR were compared with the visual estimation of an initial investigator and with the results from a reference method based on a panel of fixe experienced experts. For the 131 images of the ASTARTE protocol, the results from QUASAR were compared with those from a semi-automatic quantification system and with those from a system based on densitometric analysis. The present work validates QUASAR in a population of narrow atheromatous stenoses (> 50%). In the context of the EMMA protocol, QUASAR is not significantly different from the mean of the fixe experts. It is unbiased and more precise than the estimation of a single investigator. In the context of the ASTARTE protocol, there is no significant difference between the three methods for the stenoses higher than 50%, however, globally, QUASAR surestimates significantly (up to 10%) the degree of stenosis.     

Left ventricular remodelling and dysfunction. Can the process be prevented?

Due to continuous remodelling myocardial dysfunction is a progressive condition. Even if the initial event is so mild that it causes no immediate cardiac dysfunction (e.g. a small myocardial infarction), the remodelling process is triggered. Although the remodelling process can be adaptive, the process becomes maladaptive when the stimuli are continuous and pathological. A similar remodelling process is seen in most primary myocardial disorders, suggesting common mechanisms for the development of heart failure. Although clinical heart failure may develop acutely, for example, after an acute myocardial infarction, the progressive changes in myocardial structure and deterioration of myocardial function can go on silently for a very long time and overt heart failure may develop several years after an initial insult, even if there are no further events. In order to fundamentally improve prognosis in cardiac failure it is necessary to identify patients with an ongoing remodelling process and to effectively counteract this process as early as possible.     

Is aortic stenosis a preventable disease?

Aortic stenosis (AS) is the most common valvular disease requiring valve replacement. Its prevalence increases with age. When the severity of AS is only mild to moderate, it is well tolerated. When it becomes severe, AS confers significant morbidity and mortality. Adverse events can be avoided if it is possible to prevent or retard the progression from mild or moderate AS to severe AS. Progression of AS parallels the progression of sclerotic changes involving the aortic valve, which share histological and immunochemical similarities with the process of atherosclerosis. Far from being just a degenerative process, the development of AS is a complex and highly regulated process with a number of modifiable factors. One of the key factors appears to be lipoproteins, which are intimately involved in several pathways crucial to the development of AS. The importance of lipoproteins is further supported by epidemiological and clinical studies showing a strong association between lipoproteins and AS. The time has come to initiate prospective studies to assess the effect of cholesterol lowering on the progression of AS.