Medical hypotheses
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Oxidative stress underlies postoperative atrial fibrillation and electrophysiological remodelling associated with rapid atrial pacing. An increasing body of evidence indicates that the formation of reactive oxygen species (ROS) released following extracorporeal circulation are involved in the structural and functional myocardial impairment derived from the ischemia-reperfusion cycle. ROS behave as intracellular messengers mediating pathological processes, such as inflammation, apoptosis and necrosis, thereby participating in the pathophysiology of atrial fibrillation. ⋯ In turn, experimental studies have revealed that non-enzymatic antioxidants produce a significant functional amelioration in cardiomyocytes subjected to an oxidative challenge. Moreover, clinical studies with patients scheduled for primary coronary artery bypass graft surgery had a reduced incidence of postoperative atrial fibrillation. We present the hypothesis of non-hypoxic preconditioning based on the association of pretreatment with n-3 polyunsaturated fatty acids followed by ascorbate plus alpha-tocoferol supplementation diminishes the incidence of postoperative atrial fibrillation in patients subjected to cardiac surgery with extracorporeal circulation.
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Amniotic fluid embolism, a rare, sudden and often fatal illness of pregnancy may not be a true embolic event resulting from the physical obstruction of the pulmonary vasculature. The high degree of variability in symptoms, the lack of characteristic findings on radiological exam, the absence of a dose-response effect on symptoms, and the occasional occurrence of coagulopathies are not entirely consistent with a physical block to the circulation as the main mechanism of disease. Alternatively, it might be the result of complement activation initiated by fetal antigen leaking into the maternal circulation. ⋯ Direct measurement of serum complement as well as serum tryptase and urinary histamine are readily obtained tests in community hospitals as well as tertiary care hospitals. If the hypothesis proves true, this investigation may be of profound importance to understanding immune tolerance. Rather, than asking why one pregnant woman in 20,000 develops a violent immune reaction to the fetus, a better question is why do not all pregnant women reject the fetus which is a large collection of foreign antigens?
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Although chronic low back pain (cLBP) is increasingly recognized as a complex syndrome with multifactorial etiology, the pathogenic mechanisms leading to the development of chronic pain in this condition remain poorly understood. This article presents a new, testable pathophysiological model integrating connective tissue plasticity mechanisms with several well-developed areas of research on cLBP (pain psychology, postural control, neuroplasticity). ⋯ Non-invasive measures of connective tissue remodeling may eventually become important tools to evaluate and follow patients with cLBP in research and clinical practice. An integrative mechanistic model incorporating behavioral and structural aspects of cLBP will strengthen the rationale for a multidisciplinary treatment approach including direct mechanical tissue stimulation, movement reeducation, psychosocial intervention and pharmacological treatment to address this common and debilitating condition.
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There are common genetic mechanisms responsible for both drug effects and subsequent seeking behavior. In 1996, we coined the term Reward Deficiency Syndrome (RDS). Past and current treatment of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is considered by most to be inadequate. ⋯ Thus, in the absence of alcohol or other psychoactive drugs (dopamine releasers), especially during recovery or rehabilitation, decreasing, not increasing COMT activity, should result in enhanced synaptic dopamine as physiologically released, thereby proliferating D2 receptors while reducing stress, increasing well-being, reducing craving behavior and preventing relapse. Based on this hypothesis, we believe that adding the COMT inhibitor R. rosea (as Rhodimin) to our amino-acid and chromium combination in DUI offenders and other illegal drug-related crimes, increases the potential for more targeted neurochemical rebalancing and enhanced relapse prevention. Finally, we hypothesize that these data coupled together provide evidence that the combination of enkephalinase inhibition, neurotransmitter precursor loading, brain tryptophan enhancing and COMT inhibition as well as DNA analysis of the individual's genome, may be useful as an adjunct to therapy when used in outpatient recovery, specifically to assist in reducing craving behavior and preventing relapse.