Medical Hypotheses RSS feed: Current Issue. Aims & Scope Medical Hypotheses takes a deliberately different approach to review: the editor sees his role as a 'chooser', not a 'changer', choosing to publish what are judged to be the best papers from those submitted. The Editor sometimes uses external referees to inform his opinion on a paper, but their role is as an information source and the Editor's choice is final. The papers chosen may contain radical ideas, but may be judged acceptable so long as they are coherent and clearly expressed. The authors' responsibility for the integrity, precision and accuracy of their work is paramount. From Charlton BG. Peer usage versus peer review BMJ 2007; 335: 451 :- "Traditionally, editorial review is the main alternative to peer review. A scientist editor or editorial team applies a sieve, with varying degrees of selectivity, to research submissions. Strictly, this process should not attempt to predict whether ideas and facts are "true," because truth can be established only in retrospect. Instead, editorial selection works within constraints of subject matter on the basis of factors such as potential importance and interest, clarity and appropriateness of expression, and broad criteria of scientific plausibility. Even probably untrue papers may be judged worth publishing if they contain aspects (ideas, perspectives, data) that are potentially stimulating to the development of future science." Papers in Medical Hypotheses take a standard scientific form in terms of style, structure and referencing. The journal therefore constitutes a bridge between cutting-edge theory and the mainstream of medical and scientific communication, which ideas must eventually enter if they are to be critiqued and tested against observations. Abstracting/indexing Medical Hypotheses is indexed and abstracted in: Science Citation Index, Index Medicus/Medline, Adonis, BIOSIS, Chemical Abstracts, Elsevier BIOBASE/Current Awareness in Biological Sciences, Current Contents/Clinical Medicine, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Medical Documentation Service, Reference Update, Research Alert, SciSearch, UMI (Microfilm), Russian Academy of Sciencehttp://www.medical-hypotheses.com/?rss=yesElsevier Inc.en © 2009 Published by Elsevier Inc. All rights reserved. Medical Hypotheses0306-9877742February 2010 © 2009 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.medical-hypotheses.com/article/PIIS0306987709008123/abstract?rss=yesTitle page/Editorial Board10.1016/S0306-9877(09)00812-3Medical Hypotheses 74, 2 (2010)2010-02-01Medical Hypotheses2010-02-01742S0306-9877(09)X0013-7iihttp://www.medical-hypotheses.com/article/PIIS0306987709005271/abstract?rss=yesSummary: In UK educational circles it has long been regarded as a platitude that a good scientific education at school and undergraduate level should aim to teach critical thinking and encourage students to challenge mainstream science, debate scientific issues and express their personal opinions. However, I believe that this strategy is usually mistaken, and that such educational strategies probably do more harm than good. For most students, at most levels, for most of the time; science education should be focused on the inculcation of established knowledge. This is for the simple reason that critique is educationally-counterproductive and scientifically-worthless unless or until underpinned by adequate knowledge and competence. Instead, for the early years of science teaching, the basic assumption ought to be that the student is there to learn science; not to confront science. The basic attitude being taught should be one of humility before the science being studied.Knowledge first, critique later: Why it is a mistake for science education to encourage junior students to discuss, challenge and debate scientific knowledgeBruce G. Charlton10.1016/j.mehy.2009.07.050Medical Hypotheses 74, 2 (2010)2009-08-21Medical Hypotheses2009-08-21742S0306-9877(09)X0013-7Editorials211213http://www.medical-hypotheses.com/article/PIIS0306987709006586/abstract?rss=yesSummary: Albert Einstein once said that “The true value of a human being can be found in the degree to which he has attained liberation from the self”. For years our traditional view of ‘self’ was restricted to our own bodies; composed of eukaryote cells encoded by our genome. However, in the era of omics technologies and systems biology, this view now extends beyond the traditional limitations of our own core being to include our resident microbial communities. These prokaryote cells outnumber our own cells by a factor of ten and contain at least ten times more DNA than our own genome. In exchange for food and shelter, this symbiont provides us, the host, with metabolic functions far beyond the scope of our own physiological capabilities. In this respect the human body can be considered a superorganism; a communal group of human and microbial cells all working for the benefit of the collective – a view which most certainly attains liberation from self.The human superorganism – Of microbes and menRoy D. Sleator10.1016/j.mehy.2009.08.047Medical Hypotheses 74, 2 (2010)2009-10-16Medical Hypotheses2009-10-16742S0306-9877(09)X0013-7Editorials214215http://www.medical-hypotheses.com/article/PIIS0306987709006318/abstract?rss=yesSummary: Obsessive–compulsive disorder is characterized by obsessions that cause distress and compulsions that temporarily alleviate that distress. Despite numerous pharmacological and psychotherapeutic approaches available for treating obsessions and compulsions, their effectiveness is limited. Exploring the etiologies of obsessions reveals how obsessions develop to cause distress. It is hypothesized that the strength of obsessions can be used in a self-talk technique to reduce the frequency of compulsions. The patient would incorporate the self-talk technique while engaged in a compulsion meant to lessen the distress caused by an obsession. While performing the compulsive behavior, he or she then identifies a separate obsession, and applies a limit to stop the compulsive ritual while telling himself or herself that the second obsession will occur unless the limit is met. Although the technique has potential as a flexible tool that may be incorporated into other treatments to reduce compulsions, the therapist who chooses to use it should closely monitor its effectiveness and discontinue the technique in case of adverse effects.The potential application of obsessions to reduce compulsions in individuals with obsessive–compulsive disorderJonathan R. Scarff10.1016/j.mehy.2009.09.026Medical Hypotheses 74, 2 (2010)2009-10-15Medical Hypotheses2009-10-15742S0306-9877(09)X0013-7216218http://www.medical-hypotheses.com/article/PIIS0306987709006604/abstract?rss=yesSummary: Since the introduction of cardiac plasma troponin measurements, a significant number of patients were seen with chest pain, elevated troponin levels but no significant coronary artery disease. Pulmonary embolism, aortic valve disease, myocarditis, sepsis, trauma, arrythmias, stress cardiomyopathy and dilated cardiomyopathy stand among possible causes for this syndrome. In some cases, myocardial strain could be the mechanism underlying this phenomenon, since it is known that the stimulation of stretch-responsive integrins may lead to the release of cardiac troponin I. In the present text, a case is made in favour of classifying this syndrome, of chest pain with increased values for plasma cardiac troponin, with or without ECG changes, in the absence of definite myocardial infarction or coronary artery disease, as pseudo myocardial infarction (PMI). This constitutes a new definition for a concept with decades, formerly centered on clinical and electrocardiographic changes mimicking infarct. The case is based on the search of scientific truth, on avoidance of unnecessary cardiac examinations, on avoidance of unnecessary drug therapy and on avoidance of unnecessary legal liability. PMI should be seen as a working diagnosis, since a more definitive diagnosis can be reached at all time. It should also be seen as a heterogeneous group of patients – several different diseases and conditions can lead to this phenomenon. But it must certainly not be seen as a benign condition, since published studies point in a totally different direction.Pseudo myocardial infarction – A condition in need to be redefined?José Pedro L. Nunes10.1016/j.mehy.2009.09.041Medical Hypotheses 74, 2 (2010)2009-10-26Medical Hypotheses2009-10-26742S0306-9877(09)X0013-7219221http://www.medical-hypotheses.com/article/PIIS0306987709006380/abstract?rss=yesSummary: Mouth to mouth sexual kissing is seen in more than 90% of human cultures. Various theories have been put forward to account for this but none offer a full explanation within an evolutionary framework. As mouth to mouth sexual kissing exposes each participant to the diseases of the other, it must confer significant benefit. Human Cytomegalovirus (HCMV) is a ubiquitous infection that carries a severe teratogenic risk if primary infection is acquired during certain critical periods. As HCMV is present in salivary gland epithelial cells and sheds from periodontitis induced lesions, female inoculation with a specific male’s HCMV is most efficiently achieved through mouth to mouth contact and saliva exchange, particularly where the flow of saliva is from the male to the typically shorter female. The current hypothesis proposes that mouth to mouth sexual kissing enables females to control when they become infected with a particular male’s HCMV and so protect their offspring from the threat of teratogenesis from primary infection during vulnerable times in their development. Females only gain this benefit if they also avoid becoming infected by other males. Hence HCMV induced teratogenesis is a strong viral pressure towards the development of monogamy as well as kissing as a behavioural strategy to protect against it.Kissing as an evolutionary adaptation to protect against Human Cytomegalovirus-like teratogenesisC.A. Hendrie, G. Brewer10.1016/j.mehy.2009.09.033Medical Hypotheses 74, 2 (2010)2009-10-15Medical Hypotheses2009-10-15742S0306-9877(09)X0013-7222224http://www.medical-hypotheses.com/article/PIIS0306987709005921/abstract?rss=yesSummary: Migraine, neuropathic pain and nociceptive pain are the three commonest pain syndromes affecting human. In the present article, we first present the salient features of the pathophysiology of the three conditions particularly highlighting the core features that are similar in the three conditions. We argue on the validity of the prevailing concept that maintenance of structural integrity of the nervous system differentiates nociceptive pain from neuropathic pain and point out that the fundamental pathophysiology of lasting nociceptive pain (like cancer pain) and neuropathic pain (like nerve injury pain) is essentially same. Migraine pathophysiology is complex and complicated by two opposing views on site of migraine pain generation – peripheral versus central. We hypothesize that this dichotomy has resulted from focusing on two different sites on a single, somewhat complicated, pain mediating circuitry from the peripheral meningeal and vascular structures through several cell stations in the brain stem and thalamus up to the sensory cortical matrix. At the end, we suggest that fundamentally all the three pain syndromes referred to in the article share a common pathophysiological mechanism, namely peripheral pain perception, peripheral sensitization at dorsal root ganglion or its intracranial counterpart (like trigeminal ganglion) and central sensitization at the spinal cord (dorsal horn for somatic pain), brain stem nuclei and thalamus before final pain perception at the sensory cortical matrix.Migraine, neuropathic pain and nociceptive pain: Towards a unifying conceptA. Chakravarty, A. Sen10.1016/j.mehy.2009.08.034Medical Hypotheses 74, 2 (2010)2009-09-18Medical Hypotheses2009-09-18742S0306-9877(09)X0013-7225231http://www.medical-hypotheses.com/article/PIIS0306987709006410/abstract?rss=yesSummary: Contemporary theories to explain the autoimmune aetiology of type 1 diabetes mellitus (T1DM) include the “hygiene”, “accelerator” and “thrifty phenotype” hypotheses though none accounts for its natural history, or, epidemiology. Early-onset, T1DM is much more common in Western countries and shares features of its epidemiology with other major childhood diseases.In the autonomic denervation view, early-onset, T1DM results from injury to autonomic nerves supplying the pancreas through persistent physical efforts during defaecation in infancy. Pancreatic denervation results in loss of islets of Langerhans and reduced insulin production that may present in infancy or later life. Early introduction of cows milk and solids to the infants’ diet cause increased rates of bowel problems whereas exclusive breastfeeding in non-Western countries, protects the infant from both constipation and diarrhoea. Other important Western diseases may result from the varying effects of injuries to nerves at different sites in the autonomic nervous system.Diabetes, diet and autonomic denervationM.J. Quinn10.1016/j.mehy.2009.09.036Medical Hypotheses 74, 2 (2010)2009-10-22Medical Hypotheses2009-10-22742S0306-9877(09)X0013-7232234http://www.medical-hypotheses.com/article/PIIS030698770900440X/abstract?rss=yesSummary: General somatic afferents of facial nerve innervate skin of the concha, the posterior external ear canal and a small area behind the ear. But pain around the ear that precedes or develops at the same time as Bell’s palsy frequently is beyond the territory of sensory innervations of facial nerve. Cranial nerves are richly innervated by their own nerves called nervi nervorum that have nociceptive function. So, stimulation of nervi nervorum dominating facial nerve trunk can be transmitted to trigeminocervical nuclear complex and make referred pain on the craniofacial region segmentally. The reason why referred pain of facial nerve origin develops around the ear is that facial nerve and its ensheathing connective tissue are derivatives of second branchial arch which is homologous to the somites of body.Pain around the ear in Bell’s palsy is referred pain of facial nerve origin: The role of nervi nervorumDong-Gyun Han10.1016/j.mehy.2009.06.027Medical Hypotheses 74, 2 (2010)2009-11-26Medical Hypotheses2009-11-26742S0306-9877(09)X0013-7235236http://www.medical-hypotheses.com/article/PIIS0306987709006574/abstract?rss=yesSummary: About seven million people die of cancer every year. This is largely due to development of drug resistance, particularly multidrug resistance, in the tumor cells. Multidrug resistance (MDR) arises due to over-expression of MDR proteins in the cancer cells, which cause efflux of anticancer drugs from the cells using ATP. MDR proteins are members of the family of ABC transporters that occur universally, and are structurally and functionally conserved during evolution. In Drosophila, the germ cell attractant peptide is secreted by an ABC transport protein, mdr49. Recently, the peptide has been shown to undergo conjugation with the lipid geranylgeranyl before secretion. If conjugation with the lipid is inhibited, mdr49 protein is unable to transport the peptide. Similarly, in the case of yeast mating factor pheromone, farnesylation is required to occur before the export of the pheromone by ste6 protein, an ABC transporter. In view of the homology of mdr49 and ste6 proteins with mammalian MDR proteins, we postulate that the drug transporters also require their ligands to be conjugated to a lipid. This view finds support from the studies with synthetic inhibitors of geranylgeranyl-/farnesyl-diphosphate synthetase or transferase: The inhibitors are reported to overcome multidrug resistance in cancer cell lines or xenografts in animals. Thus, the MDR transporters also appear to require their substrates to be conjugated with a lipid. Statins are the widely used inhibitors of HMG-CoA reductase. By depleting precursors of the mevalonate pathway, statins can prevent the formation of lipids like geranylgeranyl and farnesyl. Accordingly, they should also be able to overcome multidrug resistance in cancer. A few reports in the literature indicate that they appear to do so. Statins are in wide clinical use, and their pharmacology is well known. Besides, statins per se have mild beneficial effect on the outcome of the disease. We propose that statins should be seriously investigated for their ability to overcome multidrug resistance in cancer. This should be done after careful standardization of the protocol of simultaneous treatment with anticancer drugs and a statin.Overcoming multidrug-resistance in cancer: Statins offer a logical candidateNarendra G. Mehta, Monica Mehta10.1016/j.mehy.2009.09.039Medical Hypotheses 74, 2 (2010)2009-11-02Medical Hypotheses2009-11-02742S0306-9877(09)X0013-7237239http://www.medical-hypotheses.com/article/PIIS0306987709006392/abstract?rss=yesSummary: The relative mildness of the pandemic 2009 (H1N1) swine influenza virus compared to the 1918 pandemic (H1N1) virus may be due to a variety of possible causes, including the existence of effective immunity in the host, the lessened ability of the virus to bind to target cells or to replicate in them, a diminished secretion of molecules that could cause further complications like pneumonia, etc. A comparison of the hemagglutinin sequences from the pandemic 2009 (H1N1) viruses with that of the 1918 (H1N1) virus reveals a difference in the residues occupying position 200, which has been shown to be involved in receptor binding. In all the pandemic 2009 (H1N1) hemagglutinin sequences available in the NCBI database, position 200 is occupied by serine. In the hemagglutinin of the 1918 (H1N1) virus, position 200 is occupied by proline. A proline-to-serine substitution could introduce a significant structural change in the receptor-binding site of the hemagglutinin, which could reduce the receptor-binding ability of the 2009 (H1N1) virus. It is proposed that this substitution is the cause of the relative avirulence of the 2009 (H1N1) virus compared to the 1918 (H1N1) virus.The pandemic 2009 (H1N1) swine influenza virus is mild compared to the pandemic 1918 (H1N1) virus because of a proline-to-serine substitution in the receptor-binding site of its hemagglutinin – A hypothesisEduardo A. Padlan10.1016/j.mehy.2009.09.034Medical Hypotheses 74, 2 (2010)2009-10-12Medical Hypotheses2009-10-12742S0306-9877(09)X0013-7240241http://www.medical-hypotheses.com/article/PIIS0306987709006616/abstract?rss=yesSummary: Prostate cancer (CaP) is one of the most common types of cancer among men and the second leading cause of cancer-related death in western countries. The risk factors for CaP are age, race/ethnicity, family history and diet. It is interesting that epidemiologic evidence suggests a history of diabetes mellitus (DM) is related to a decreased CaP risk. The cause of this association remains largely unknown. DM is a group of metabolic diseases characterized by hyperglycemia and insulin resistance. It is commonly associated with microvascular complications including diabetic retinopathy, nephropathy and neuropathy. The typical histological changes of microvascular lesions are capillary basement membrane thickening, capillary occlusion and degeneration, eventually capillary dysfunction and organ ischemia. Therefore, we hypothesize that DM might induce local microvascular dysfunction and prostate ischemia, which prevent initiation and development of CaP. Currently, numerous studies showing effect of anti-angiogenesis therapy on CaP strongly support our hypothesis.Why does diabetes offer protective effects against prostate cancer? The possible role of its microvascular complicationsWeiwei Zhang, Renming Hu10.1016/j.mehy.2009.09.042Medical Hypotheses 74, 2 (2010)2009-10-28Medical Hypotheses2009-10-28742S0306-9877(09)X0013-7242243http://www.medical-hypotheses.com/article/PIIS0306987709006367/abstract?rss=yesAbstract: Mass hysteria or collective hysteria usually begins when an individual shows a hysteric manifestation in front of others in the same group who later contagiously acquire the same symptoms. The underlying pathogenesis of mass hysteria is still unknown. It has been demonstrated that the mirror neuron system (MNS) provides an important neural substrate for humans’ ability to imitate and there is an inhibitive component of MNS keeping us from imitating everything we see. We proposed that the inhibitive component for MNS automatic imitation may not function well in individuals of the group that results in the outbreaks of mass hysteria. We also provide evidences from emotional contagion, gender difference and treatment in mass hysteria to support this hypothesis.The mirror neuron system may play a role in the pathogenesis of mass hysteriaYao-Tung Lee, Shih-Jen Tsai10.1016/j.mehy.2009.09.031Medical Hypotheses 74, 2 (2010)2009-10-08Medical Hypotheses2009-10-08742S0306-9877(09)X0013-7244245http://www.medical-hypotheses.com/article/PIIS0306987709006343/abstract?rss=yesSummary: In human pregnancies, maternal absorption of iron is markedly curtailed in the first trimester. In a murine model, iron was teratogenic in the analogous embryonic period. Although iron is a weak mutagen, it is a powerful oxidant and a catalyst of formation of hydroxyl radicals. Studies are needed to determine if there might be an association of first trimester iron supplementation with miscarriage/fetal abnormalities.First trimester curtailment of iron absorption: Innate suppression of a teratogen?E.D. Weinberg10.1016/j.mehy.2009.09.029Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7246247http://www.medical-hypotheses.com/article/PIIS030698770900632X/abstract?rss=yesSummary: Transient Loss Of Consciousness (TLOC) or vasovagal syncope is well known phenomenon in dental/maxillofacial surgery. Despite considerable study of vasovagal syncope, its pathophysiology remains to be fully elucidated. After having encountered a case of trigeminocardiac reflex after extraction of maxillary first molar we observed and studied 400 extractions under local anesthesia to know the relation between trigeminocardiac reflex and syncope. We make hypothesis that trigeminocardiac reflex which is usually seen under general anesthesia when all sympathetic reflexes are blunted can also occur under local anesthesia during extractions of maxillary molars (dento-cardiac reflex) and mediate syncope.A new hypothesis of cause of syncope: Trigeminocardiac reflex during extraction of teethGururaj Arakeri, Veena Arali10.1016/j.mehy.2009.09.027Medical Hypotheses 74, 2 (2010)2009-10-08Medical Hypotheses2009-10-08742S0306-9877(09)X0013-7248251http://www.medical-hypotheses.com/article/PIIS0306987709006306/abstract?rss=yesAbstract: Myopia is a major threat for vision health across the world. Around 1 in 4 in the West and over 3 in 4 in the East are suffering from this common eye disorder. It is a complex trait affected by both genetic and environmental determinants. Axial length is an essential man-made parameter generated from ocular biometric components. It represents a combination of anterior chamber depth, lens thickness and vitreous chamber depth. Meanwhile, it is an endophenotype of the phenotype of myopia. In the mainstream genetic studies on vision science, it is always treated only as a parameter rather than an endophenotype. However, in this article, the potential advantages are discussed for axial length analysed as an endophenotype independently. It may provide solutions for the exploration of myopia genetics.Axial length: An underestimated endophenotype of myopiaWeihua Meng, Jacqueline Butterworth, Francois Malecaze, Patrick Calvas10.1016/j.mehy.2009.09.025Medical Hypotheses 74, 2 (2010)2009-11-05Medical Hypotheses2009-11-05742S0306-9877(09)X0013-7252253http://www.medical-hypotheses.com/article/PIIS030698770900629X/abstract?rss=yesSummary: Despite theoretical and experimental efforts to model neuronal networks, the origin of cerebral cognitive functions and memory formation are still unknown. Recently, we have proposed that in addition to chemical and electrical signals, the cellular components of the neocortex (especially neurons and astrocytes) may communicate with each other through magnetic signals generated by themselves. This magnetic communication would be the ground of short-term memory. In the present paper, we propose that brain magnetite may be a component of the mechanisms, conserved during evolution, to detect and transduce magnetic fields generated inside the cerebral neocortex. Specifically, we propose a possible role for magnetite nanoparticles, distributed through neuronal and astroglial membranes, in perception, transduction and storage of information that arrives to the neocortex.Long-term memory in brain magnetiteMarcos Arturo Martínez Banaclocha, István Bókkon, Helios Martínez Banaclocha10.1016/j.mehy.2009.09.024Medical Hypotheses 74, 2 (2010)2009-10-08Medical Hypotheses2009-10-08742S0306-9877(09)X0013-7254257http://www.medical-hypotheses.com/article/PIIS0306987709006276/abstract?rss=yesSummary: Non-invasive molecular analysis of fetal DNA is the diagnostic goal of prenatal medicine. Circulating fetal DNA can be detected in maternal plasma. Recently, it has been detected in the urine of pregnant women. We hypothesize that fetal DNA is present also in maternal saliva and that advances in stabilization and isolation of nucleic acids from saliva enable non-invasive and repeated sampling for prenatal diagnostics. The hypothesis is testable using saliva samples of pregnant women with confirmed male fetuses. Y-specific sequences should be detectable in salivary DNA. Caution must be given to the prevention of contamination. If proved in large studies, the presence of fetal DNA fragments in maternal saliva would enable a wide range of applications in prenatal medicine.Does maternal saliva contain fetal DNA usable for prenatal diagnostics?Barbora Vlková, Tomáš Szemes, Gabriel Minárik, Ján Turňa, Peter Celec10.1016/j.mehy.2009.09.022Medical Hypotheses 74, 2 (2010)2009-10-08Medical Hypotheses2009-10-08742S0306-9877(09)X0013-7258260http://www.medical-hypotheses.com/article/PIIS0306987709006240/abstract?rss=yesSummary: How might homosexual orientation have evolved and been maintained? Several adaptationist explanations have been examined in attempt to reconcile the presence of same-sex sexual behaviors with traditional selection-based theory, showing little empirical support. The current paper presents a novel adaptationist explanation for the evolution and maintenance of same-sex sexual behaviors in males, both between- and within-species, related to the evolution of anisogamy. Under conditions of isogamy, sexual reproduction occurs between individuals with gametes of similar morphology. With the evolution of anisogamy came greater specificity on the types of individuals that would produce offspring when mated with (i.e. those with opposing gamete sizes). It is suggested that with this evolutionary change, a specified psychological adaptation orienting individuals primarily towards mating partners with newly opposing gamete sizes was then selected for. It is thus hypothesized that sexual orientation will vary along the anisogamy–isogamy continuum, with homosexual orientation being associated with closer approximations towards isogamy. This hypothesis leads to two specific predictions. First, in comparisons between species, the presence of same-sex sexual behaviors will be more likely to occur as sperm to egg ratios approach 1:1. Second, in comparisons within species, those individuals with greater sperm lengths will be more likely to exhibit same-sex sexual behaviors than those with lesser sperm lengths. Examination of the present hypothesis stands to greatly increase our knowledge of the selective forces shaping both biological and psychological evolution.Sexual orientation in males and the evolution of anisogamyLawrence Ian Reed10.1016/j.mehy.2009.09.019Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7261263http://www.medical-hypotheses.com/article/PIIS0306987709006239/abstract?rss=yesSummary: Evidence is provided supporting the hypothesis that the much improved prognosis for younger women with diminished oocyte reserve compared to women of advanced reproductive age is related to a difference in mechanism for oocyte depletion. For younger women the majority have had destruction of certain portions of their ovarian tissue but the remaining spared ovarian tissue has proportionately the same percentage of normal follicles as their age peers. The hypothesis continues that some factor that is responsible for earlier development of primary to antral follicles persists with the early conceptus and protects it from early programmed cell death. Thus by natural selection most women of advanced reproductive age have oocytes that fertilize normally and produce normal morphologic embryos, but lacking this apoptosis inhibiting factor dies very early between days 6 and 12 from fertilization.Evidence that oocyte quality in younger women with diminished oocyte reserve is superior to those of women of advanced reproductive ageJ.H. Check, R. Cohen10.1016/j.mehy.2009.09.018Medical Hypotheses 74, 2 (2010)2009-10-21Medical Hypotheses2009-10-21742S0306-9877(09)X0013-7264267http://www.medical-hypotheses.com/article/PIIS0306987709006227/abstract?rss=yesSummary: Bioindicators of ecosystem health, such as ant (Hymenoptera: Formicidae) diversity, reflect the ultimate (evolutionary) drivers of ecosystem function. Surveillance data on human population health, such as the frequency of ant stings, also provide a useful bioindicator of ecosystem health in so far as the presence of imported, stinging, pest species reflects the proximate (mechanistic) drivers of ecosystem function. The relationship between human health surveillance data and the ultimate drivers of ecosystem function has however not been studied at a research level. The possible integrated use of such apparently disparate data may offer a new tool to help manage our environment sustainably for the concurrent benefit of both ecosystem health and human health. Productive directions for research in this field are likely to lie in areas where disease outcomes are dependent on environmental intermediaries, such as vector borne or water borne infectious diseases, and the paper provides one worked example using allergy to ant stings as a case study.Can human health outcomes be used as bioindicators of ecosystem function?Philip Weinstein10.1016/j.mehy.2009.09.017Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7268269http://www.medical-hypotheses.com/article/PIIS0306987709006215/abstract?rss=yesSummary: Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws.The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.Thermodynamic laws apply to brain functionAlen J. Salerian10.1016/j.mehy.2009.09.016Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7270274http://www.medical-hypotheses.com/article/PIIS0306987709006203/abstract?rss=yesSummary: Recent studies by Varricchio et al. reveal that males cared for the eggs of troodontids and oviraptorids, so-called “non-avian theropods” of the Cretaceous, just as do those of most Paleognathic birds (ratites and tinamous) today. Further, the clutches of both groups have large relative volumes, and consist of many eggs of relatively large size. By comparison, clutch care by most extant birds is biparental and the clutches are of small relative volume, and consist of but few small eggs. Varricchio et al. propose that troodontids and oviraptorids were pre-avian and that paternal egg care preceded the origin of birds. On the contrary, unmentioned by them is that abundant paleontological evidence has led several workers to conclude that troodontids and oviraptorids were secondary flightless birds. This evidence ranges from bird-like bodies and bone designs, adapted for climbing, perching, gliding, and ultimately flight, to relatively large, highly developed brains, poor sense of smell, and their feeding habits. Because ratites also are secondarily flightless and tinamous are reluctant, clumsy fliers, the new evidence strengthens the view that troodontids and oviraptorids were secondarily flightless.Although secondary flightlessness apparently favors paternal care of clutches of large, abundant eggs, such care is not likely to have been primitive. There are a suite of previously unknown independent findings that point to the evolution of, first, maternal, followed by biparental egg care in earliest ancestors of birds. This follows from the discovery of remarkable relict avian reproductive behaviors preserved by virtue of the highly conservative nature of vertebrate brain evolution. These behaviors can be elicited readily by exposing breeding birds to appropriate conditions, both environmental and with respect to their eggs and chicks. They give significant new clues for a coherent theory of avian origin and early evolution.Secondarily flightless birds or Cretaceous non-avian theropods?J. Lee Kavanau10.1016/j.mehy.2009.09.015Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7275276http://www.medical-hypotheses.com/article/PIIS0306987709006173/abstract?rss=yesSummary: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, characterised by poorly reversible, obstructive airflow limitation. Alongside other comorbidities, COPD is associated with increased morbidity and mortality resulting from cardiovascular disease – mainly heart failure and ischemic heart disease. Both diseases share an important risk factor, namely, smoking. About 50% of COPD patients are active cigarette smokers.Bronchodilation is the cornerstone of pharmaceutical treatment for COPD symptoms, and half of all COPD patients use long-acting bronchodilating agents. Discussion about these agents is currently focusing on the association with overall mortality and morbidity in COPD patients, of cardiovascular origin in particular.Bronchodilation diminishes the hyperinflated state of the lung and facilitates the pulmonary deposition of cigarette smoke by deeper inhalation into the smaller airways. Smaller particles, as in smoke, tend to penetrate and depose more in these small airways. In addition, bronchodilation indeed increases carbon monoxide uptake in the lungs, an important gaseous compound of cigarette smoke. Since the number of cigarettes smoked is positively correlated to mortality from cardiac events, we therefore hypothesise that chronic bronchodilation increases cardiovascular disease and mortality in COPD patients who continue smoking by increasing pulmonary retention of pathogenic smoke constituents. Indeed, a recent meta-analysis is suggestive that long-acting anticholinergics might increase cardiovascular disease if patients exceed a certain number of cigarettes smoked.To demonstrate the fundamental mechanism of this pathogenic interaction we will perform a randomised placebo-controlled cross-over trial to investigate the effect of maximum bronchodilation on the retention of cigarette smoke constituents. In 40 moderate to severe COPD patients we measure the inhaled and exhaled amount of tar and nicotine, as well during maximum bronchodilation as during administration of placebo. The fraction of retention of tar and nicotine is subsequently calculated for both circumstances and analysed for association with bronchodilation. Further observational cohort studies or randomised clinical trials designed to monitor cardiovascular events may well evaluate the interaction. Since many patients are at risk for this possibly hazardous interaction, its relevance to our society and healthcare is potentially great. The implication will be that the urgency to quit smoking is intensified. Besides, chronic bronchodilation – specifically long-acting bronchodilators – needs to be discouraged in smoking COPD patients that refuse to quit.Interaction in COPD experiment (ICE): A hazardous combination of cigarette smoking and bronchodilation in chronic obstructive pulmonary diseaseW.D. van Dijk, Y. Heijdra, P.T.J. Scheepers, J.W.M. Lenders, C. van Weel, T.R.J. Schermer10.1016/j.mehy.2009.09.012Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7277280http://www.medical-hypotheses.com/article/PIIS0306987709006161/abstract?rss=yesSummary: Evidence supports the premise that alpha7 nicotinic acetylcholine receptors in the central nervous system, sometimes referred to as neuronal nicotinic receptors (NNRs), play a central role in the development of Alzheimer’s disease (AD) pathophysiology. Moreover, these receptors may represent the key to unifying aspects of the cholinergic hypothesis of AD with many of the apparently disparate mechanisms such as β-amyloid deposition, tau hyperphosphorylation, and ApoE4 abnormalities variously proposed to underlie the progression of the disease. We hypothesize that neuronal degeneration in incipient AD is the result of coincident events involving, at their core, deficits in alpha7 NNR function. The resulting hypocholinergic tone could potentially have serious consequences since alpha7 NNRs are known to modulate fundamental pathways involved in cell survival such as JAK2-STAT3. This hypothesis predicts that any factors that compromise alpha7 function have the potential to negatively impact neuronal viability. For example, such factors could include deficits in the primary neurotransmitter acetylcholine (ACh), underactivity of normal cognitive processes that stimulate alpha7 NNRs (i.e., use-dependency), or the reported binding of β-amyloid and ApoE4 to alpha7 NNRs, all of which could effectively decouple the receptors from key pro-survival pathways. Since these pathways are known to negatively modulate GSK-3β, which regulates tau phosphorylation, downstream effects such as tau hyperphosphorylation would be expected to arise. Conversely, the maintenance of normal alpha7 NNR activity by adequate levels of ACh or other NNR agonists would be expected to support normal cholinergic tone, prevent the binding of β-amyloid and ApoE4 and preserve the integrity of the neurons. We therefore propose that decreased cholinergic tone is at the apex of AD pathophysiology, with factors such as β-amyloid and ApoE4 playing a contributory role rather that a causal one and hyperphosphorylation of tau representing a detector of concomitant hypocholinergic tone and β-amyloid deposition. Thus the convergence of β-amyloid deposition and/or ApoE4 binding and co-localization with alpha7 NNRs, which are favored under conditions of low cholinergic tone, and the downstream cascade of tau hyperphosphorylation through disinhibition of GSK-3β appear to explain and reconcile many of the discordant findings in this very active area of CNS research.Alpha7 neuronal nicotinic receptors: The missing link to understanding Alzheimer’s etiopathology?Merouane Bencherif, Patrick M. Lippiello10.1016/j.mehy.2009.09.011Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7281285http://www.medical-hypotheses.com/article/PIIS030698770900615X/abstract?rss=yesSummary: Over the past four decades, it was found that folic acid supplementation produced an antidepressant-like effect mediated by interaction with the brain noradrenergic receptors (inhibitory effect) and serotonergic receptors (stimulatory effect). Hot flushes occur in postmenopausal women because of disturbances in the thermoregulatory centre, most likely as a result of estrogen deficiency-related increase in central noradrenergic activity and reduced serotonergic activity. Therefore, we hypothesize that folic acid supplementation may ameliorate hot flushes by the same mechanism as estrogen replacement, i.e., by interacting with monoamine neurotransmitters in the brain; namely norepinephrine and serotonin. This article discusses the hypothesis and presents supportive preliminary data.Folic acid supplementation cures hot flushes in postmenopausal womenSherief Gaweesh, Ayman A.A. Ewies10.1016/j.mehy.2009.09.010Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7286288http://www.medical-hypotheses.com/article/PIIS0306987709006148/abstract?rss=yesSummary: Discussions around the etiology of autoimmune disease routinely focus on the interplay between genes and the environment. In turn, efforts to ameliorate these diseases seek to modify genetic and environmental factors. However, there may be a third element that also accounts for the progression of autoimmunity. This article explores the role of chance, exemplified by the stochastic process of immune repertoire generation, in the evolution of autoimmunity. The presented modeling studies and concepts suggest that chance plays as significant a role as genes or environment. This hypothesis implies that a full understanding of the role of genes and environment will also require investigators to account for stochastic processes in building comprehensive disease models.Accounting for chance in the calculus of autoimmune diseaseDaniel J. Moore10.1016/j.mehy.2009.09.009Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7289293http://www.medical-hypotheses.com/article/PIIS0306987709006094/abstract?rss=yesSummary: An analysis is carried out of a set of psychic phenomena appearing always in the same way: an experience suddenly invades the consciousness, unfolding automatically and with great intensity. This psychic automatism, of which the patient is a passive observer, is accompanied by an overwhelming feeling of strangeness. Our hypothesis is that these phenomena are the expression of partial seizures with a psychic content. A comparative study is then made of the phenomenology of these partial seizures with a psychic content, on the one hand, and of that of positive syndrome of schizophrenia, on the other. It reveals a wealth of clinical information indicating an overlap between the two conditions. This inclines us to postulate of an existence of shared etiopathogenic mechanisms for both pathologies.Positive syndrome of schizophrenia and epilepsyIria Alvarez-Silva, Sergio Alvarez-Silva, Javier Alvarez-Rodriguez10.1016/j.mehy.2009.09.004Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7294296http://www.medical-hypotheses.com/article/PIIS0306987709006082/abstract?rss=yesAbstract: There is growing interest in the concept of network pharmacology, as opposed to specific pharmacological targets, as an important drug discovery paradigm. Also known as the “magic shotgun” paradigm, this strategy involves individual drugs interacting with multiple targets to achieve clinical benefit. Pharmacological promiscuity consistent with this paradigm has been suggested in vitro for antidepressants and anticonvulsants, which interact with many classes of ion channels (among other receptor targets). Although the link between certain “off-target” interactions and drug side effects is well-accepted, the potential linkage between promiscuity and clinical efficacy remains poorly understood. Here we summarize interactions of clinically useful anti-psychotic and anti-dementia medications with a diverse array of ligand- and voltage-gated ion channels. We hypothesize that promiscuous ion channel modulation may contribute to the efficacy of drugs used to treat psychosis and dementia.Promiscuous modulation of ion channels by anti-psychotic and anti-dementia medicationsMatt T. Bianchi10.1016/j.mehy.2009.09.003Medical Hypotheses 74, 2 (2010)2009-09-28Medical Hypotheses2009-09-28742S0306-9877(09)X0013-7297300http://www.medical-hypotheses.com/article/PIIS0306987709006070/abstract?rss=yesSummary: Malignant tumor hypoxia, which occurs due to abnormal and poor circulation of the tumoral vasculature, is the major cause of tumor aggressivity and failure of oncology therapeutics, particularly radiotherapy. Indeed, radio-sensitivity is reduced up to 3-fold in tumoral tissues with a lower oxygen partial pressure (PtO2). As such, there is no efficient means for increasing tumor PtO2 during radiotherapy sessions.Through a concept called “arterial flow focalization”, by controlled temporary endo or peri-vascular occlusion of the collateral arterial branch(es) upstream of the tumor (organ), it is possible to redirect blood flow through the principal artery of the downstream tumor (organ), thereby increasing tumor arterial flow, and hence oxygen supply, thus increasing tumor PtO2 at the desired intensity and timing, in synchrony with radiotherapy, and greatly improving radiosensitivity. Chemotherapy and photodynamic therapy efficacy could be also be increased, by increasing the PtO2 and by improvement of tumor blood perfusion and hence drug delivery to the tumor.Furthermore, controlled focalization of arterial flow could be used in all necrotic disease processes, particularly fulminant hepatitis, to stimulate hepatocyte regeneration, not only through hyper-oxygenation, but also through triggering of endothelial shear stress in the sinusoidal wall.Arterial flow focalization could increase tissue oxygen partial pressure, or trigger endothelial shear stress – A new concept to overcome cancer hypoxia-induced radiotherapy resistance, or stimulate liver regeneration during fulminant hepatitisJulien Reyal10.1016/j.mehy.2009.09.002Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7301308http://www.medical-hypotheses.com/article/PIIS0306987709006069/abstract?rss=yesAbstract: Organophosphorus (OP) pesticide self-poisoning is a major clinical problem in rural Asia and it results in the death of 200,000 people every year. At present, it is lack of effective methods to treat severe organophosphate poisoning. The high mortality rate lies on the amount of toxic absorption. Intravenous lipid emulsions can be used as an antidote in fat-soluble drug poisoning. The detoxification mechanism of intravenous lipid emulsions is “lipid sink”, which lipid emulsions can dissolve the fat-soluble drugs and separate poison away from the sites of toxicity. Most of organophosphorus pesticides are highly fat-soluble. So, intravenous lipid emulsions have the potentially clinical applications in treatment of OP poisoning. Extracorporeal blood purification especially charcoal hemoperfusion is an efficient way to eliminate the poison contents from the blood. We hypothesize that the combination of intravenous lipid emulsions and charcoal hemoperfusion can be used to cure severe organophosphate poisoning. This novel protocol of therapy comprises two steps: one is obtained intravenous access to infuse lipid emulsions as soon as possible; another is that charcoal hemoperfusion will be used to clear the OP substances before the distribution of OP compounds in tissue is not complete. The advantages of this strategy lie in three points. Firstly, it will alleviate the toxic effect of OP pesticide in the patients by isolation and removal the toxic contents. Secondly, the dosage of antidotes can be reduced and its side-effects will be eased. Thirdly, a large bolus of fatty acids provide energy substrate for the patients who are nil by mouth. We consider that it would become a feasible, safe and efficient detoxification intervention in the alleviation of severe organophosphate poisoning, which would also improve the outcome of the patients.Intravenous lipid emulsions combine extracorporeal blood purification: A novel therapeutic strategy for severe organophosphate poisoningYaguang Zhou, Chengye Zhan, Yongsheng Li, Qiang Zhong, Hao Pan, Guangtian Yang10.1016/j.mehy.2009.09.001Medical Hypotheses 74, 2 (2010)2009-09-28Medical Hypotheses2009-09-28742S0306-9877(09)X0013-7309311http://www.medical-hypotheses.com/article/PIIS0306987709006057/abstract?rss=yesSummary: Benign prostatic hyperplasia (BPH) is a common disease of the aged. And its etiopathogenesis is still uncertain after centuries’ research. Ducts of prostate were often found obstructed and ectasy in pathological examinations. Recent studies suggest that pressure can facilitate the proliferation of prostatic cells. Therefore we hypothesize that ductal obstruction can induce augmentation of intraductal pressure and facilitate the proliferation of prostatic cells. Ductal obstruction might play a role in the etiopathogenesis of BPH. If our hypothesis can be further supported by future researches, it may change the present etiopathogenesis theory of BPH as well as the treatment strategies of it.Duct obstruction: The possible etiopathogenesis of benign prostatic hyperplasiaRuzhu Lan, Zhangqun Ye10.1016/j.mehy.2009.08.042Medical Hypotheses 74, 2 (2010)2009-09-16Medical Hypotheses2009-09-16742S0306-9877(09)X0013-7312313http://www.medical-hypotheses.com/article/PIIS0306987709006045/abstract?rss=yesSummary: Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the inherited renal cystic diseases and constitutes 10% of the end stage kidney disease population. ADPKD is caused by PKD1 and PKD2 gene mutations in 85% and 15% of the cases respectively. Its high prevalence and negative impact on health outcomes fostered efforts to explain pathophysiologic pathways of cyst formation in kidneys. Among these are increased apoptosis, unopposed proliferation of tubule cells, impaired polarization and planar cell polarity, impaired cAMP pathway, cilier dysfunction, activated mTOR pathway, increased tumor necrosis factor-alpha (TNF-α) production. Many drugs have been tried in an attempt to halt cystogenesis in some point. Despite success to some extent in experimental studies, none reached clinical armamentarium yet. Colchicine, originally extracted from Colchicum autunale, is an anti-inflammatory drug that has been in continuous use for more than 3000years. It has been used successfully to prevent attacks of familial mediterranien fever and amyloidosis, to treat gout and pseudogout attacks for a few decades. Colchicine principally is a microtubule inhibitor, thus prevents cell migration, division, and polarization. It also has anti-apoptotic, anti-proliferative and anti-inflammatory effects and down-regulates (TNF-α) receptors. As can easily be seen, many of the effects of colchicine have pathophysiologic counterparts in ADPKD. Thus, we hypothesized that colchicine would be beneficial to prevent or at least delay cyst formation in ADPKD patients. Indirect evidence also support our hypothesis, in which taxol and paclitaxel, other two microtubule inhibitors, were shown to delay cyst formation in experimental models of ADPKD. To our opinion, despite its narrow therapeutic index, widespread experience makes colchicine a suitable candidate for prolonged clinical use, should experimental studies show any benefit in ADPKD.Colchicine treatment in autosomal dominant polycystic kidney disease: Many points in commonYalcin Solak, Huseyin Atalay, Ilker Polat, Zeynep Biyik10.1016/j.mehy.2009.08.041Medical Hypotheses 74, 2 (2010)2009-09-18Medical Hypotheses2009-09-18742S0306-9877(09)X0013-7314317http://www.medical-hypotheses.com/article/PIIS0306987709006033/abstract?rss=yesSummary: The adverse health effects of environmental contaminants (ECs) are a rising public health concern, and a major threat to sustainable socioeconomic development. The developing fetuses and growing children are particularly vulnerable to the adverse effects of ECs. However, assessing the health impact of ECs presents a major challenge, given that multiple outcomes may arise from one exposure, multiple exposures may result in one outcome, and the complex interactions between ECs, and between ECs, nutrients and genetic factors, and the dynamic temporal changes in EC exposures during the life course. Large-scale prospective birth cohort studies collecting extensive data and specimen starting from the prenatal or pre-conception period, although costly, hold promise as a means to more clearly quantify the health effects of ECs, and to unravel the complex interactions between ECs, nutrients and genotypes. A number of such large-scale studies have been launched in some developed counties. We present an overview of “why”, “what” and “how” behind these efforts with an objective to uncover major unidentified limitations and needs. Three major limitations were identified: (1) limited data and bio-specimens regarding early life EC exposure assessments in some birth cohort studies; (2) heavy participant burdens in some birth cohort studies may bias participant recruitment, and risk substantial loss to follow-up, protocol deviations limiting the quality of data and specimens collection, with an overall potential bias towards the null effect; (3) lack of concerted efforts in building comparable birth cohorts across countries to take advantage of natural “experiments” (large EC exposure level differences between countries) for more in-depth assessments of dose–response relationships, threshold exposure levels, and positive and negative effect modifiers. Addressing these concerns in current or future large-scale birth cohort studies may help to produce better evidence on the health effects of ECs.Large prospective birth cohort studies on environmental contaminants and child health – Goals, challenges, limitations and needsZhong-Cheng Luo, Jian-Meng Liu, William D. Fraser10.1016/j.mehy.2009.08.044Medical Hypotheses 74, 2 (2010)2009-09-18Medical Hypotheses2009-09-18742S0306-9877(09)X0013-7318324http://www.medical-hypotheses.com/article/PIIS0306987709005994/abstract?rss=yesAbstract: Supercritical carbon dioxide (CO2) possesses germicide (bactericide and sporicide) effect. Despite of the fact, that this effect is used in industrial sterilization processes, the sterilization mechanism at molecular level is unclear. Our hypotheses can provide a molecular-biological explanation for the phenomenon.We believe that in supercritical state CO2 reacts competitively with Met-tRNAfMet, the formation rate and the amount of formyl-methionyl-tRNA (fMet-tRNAfMet) will be diminished by irreversible substrate consumption. The fMet-tRNAfMet possesses a key role in prokaryotic protein synthesis, being almost exclusively the initiator aminoacyl-tRNA. The formed carbamoyl-methionyl-tRNA (cMet-tRNAfMet), probably stable only under pressure and high CO2 concentration, is stabilized by forming a ternary molecular complex with the GTP-form of the translational initiation factor 2 (GTP-IF2). This complex is unable to dissociate from preinitiation 70S ribosomal complex because of strong polar binding between the protein C-2 domain and the modified initiator aminoacyl-tRNA. The IF2-fMet-tRNAfMet-blocked 70S ribosomal preinitiation complex does not decompose following the GTP hydrolysis, becoming unable to synthesize proteins. The death of the microbial cell is caused by inhibition of the protein synthesis and energetic depletion. Moreover, we propose a possible mechanism for the accumulation of cMet-tRNAfMet in the bacterial cell.Since the translational process is an important target for antibiotics, the proposed mechanism could be a work hypothesis for discovery of new antibiotics. Made by high conservative character of prokaryotic translation initiation, the proposed IF2 pathway deterioration strategy may conduct to obtaining selective (with low mammalian toxicity) antimicrobials and at the same time, with reduced possibility of the drug resistance development.A possible explanation of the germicide effect of carbon dioxide in supercritical state based on molecular-biological evidenceCsaba D. András, Csaba Csajági, Csongor K. Orbán, Csilla Albert, Beáta Ábrahám, Ildikó Miklóssy10.1016/j.mehy.2009.08.043Medical Hypotheses 74, 2 (2010)2009-09-18Medical Hypotheses2009-09-18742S0306-9877(09)X0013-7325329http://www.medical-hypotheses.com/article/PIIS0306987709005970/abstract?rss=yesSummary: Heterotopic ossification (HO) is a frequent complication after musculoskeletal trauma and surgical procedures. It usually decreases joint mobility and eventually causes loss of joint function. However, there is no satisfied treatment available for HO. Lipopolysaccharide (LPS) is traditionally recognized as an endotoxin. Recently, studies found LPS was associated with loss of bone during bacterial infection and periprosthetic osteolysis after total joint replacement. Cell and molecular biology studies further found that LPS initiated the osteoclast formation, stimulated osteoclast activity and inhibited osteoblast differentiation. Given HO is an abnormality in bone modeling which increases bone mass within extraskeletal soft tissues, we herein hypothesize that local LPS injection might be a potential novel treatment for HO.Local lipopolysaccharide injection: A potential novel treatment for heterotopic ossificationDe-Ting Xue, Qiang Zheng, Hang Li, Zhi-Jun Pan10.1016/j.mehy.2009.08.038Medical Hypotheses 74, 2 (2010)2009-09-16Medical Hypotheses2009-09-16742S0306-9877(09)X0013-7330331http://www.medical-hypotheses.com/article/PIIS0306987709005969/abstract?rss=yesSummary: The neural control of the cardiovascular system is a complex process that involves many structures at different levels of nervous system. Several cortical areas are involved in the control of systemic blood pressure, such as the sensorimotor cortex, the medial prefrontal cortex and the insular cortex.Non-invasive brain stimulation techniques – repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) – induce sustained and prolonged functional changes of the human cerebral cortex. rTMS and tDCS has led to positive results in the treatment of some neurological and psychiatric disorders. Because experiments in animals show that cortical modulation can be an effective method to regulate the cardiovascular system, non-invasive brain stimulation might be a novel tool in the therapeutics of human arterial hypertension. We here review the experimental evidence that non-invasive brain stimulation can influence the autonomic nervous system and discuss the hypothesis that focal modulation of cortical excitability by rTMS or tDCS can influence sympathetic outflow and, eventually, blood pressure, thus providing a novel therapeutic tool for human arterial hypertension.Non-invasive brain stimulation for the management of arterial hypertensionF. Cogiamanian, A.R. Brunoni, P.S. Boggio, F. Fregni, M. Ciocca, A. Priori10.1016/j.mehy.2009.08.037Medical Hypotheses 74, 2 (2010)2010-02-01Medical Hypotheses2010-02-01742S0306-9877(09)X0013-7332336http://www.medical-hypotheses.com/article/PIIS0306987709005799/abstract?rss=yesSummary: The slow spread of residential electrification in the US in the first half of the 20th century from urban to rural areas resulted by 1940 in two large populations; urban populations, with nearly complete electrification and rural populations exposed to varying levels of electrification depending on the progress of electrification in their state. It took until 1956 for US farms to reach urban and rural non-farm electrification levels. Both populations were covered by the US vital registration system. US vital statistics tabulations and census records for 1920–1960, and historical US vital statistics documents were examined. Residential electrification data was available in the US census of population for 1930, 1940 and 1950. Crude urban and rural death rates were calculated, and death rates by state were correlated with electrification rates by state for urban and rural areas for 1940 white resident deaths. Urban death rates were much higher than rural rates for cardiovascular diseases, malignant diseases, diabetes and suicide in 1940. Rural death rates were significantly correlated with level of residential electric service by state for most causes examined. I hypothesize that the 20th century epidemic of the so called diseases of civilization including cardiovascular disease, cancer and diabetes and suicide was caused by electrification not by lifestyle. A large proportion of these diseases may therefore be preventable.Historical evidence that electrification caused the 20th century epidemic of “diseases of civilization”Samuel Milham10.1016/j.mehy.2009.08.032Medical Hypotheses 74, 2 (2010)2009-09-14Medical Hypotheses2009-09-14742S0306-9877(09)X0013-7337345http://www.medical-hypotheses.com/article/PIIS0306987709005787/abstract?rss=yesSummary: Lung cancer continues to be the leading cause of cancer deaths worldwide. Cigarette smoking is the predominant cause of lung cancer. Researchers found that tobacco-induced molecular changes in the oral epithelium are similar to those in the lung epithelium. Furthermore, there has been considerable progress in investigating the tumorigenesis of oral epithelium using molecular markers. These results offer hope that we can predict lung cancer in smokers by oral examination, which is much easier and more practical than lung biopsy. The hypothesis is to collect oral epithelial cells by gently scraping the oral mucosa, and analyze the DNA variation in these cells using molecular biological methods. Therefore, the oral epithelium is serving as a surrogate tissue for assessing smoking-induced molecular damage to the lungs and thus have important implications for early detection of lung cancer.Detection of lung cancer by oral examinationZhonghua Xiong, Guanze Xiong, Yi Man, Lichun Wang, Wei Jing10.1016/j.mehy.2009.08.030Medical Hypotheses 74, 2 (2010)2009-09-16Medical Hypotheses2009-09-16742S0306-9877(09)X0013-7346347http://www.medical-hypotheses.com/article/PIIS0306987709005775/abstract?rss=yesSummary: Although peripartum cardiomyopathy (PPCM) is a rare disease, it has very serious consequences for both mother and child. No single cause has been held responsible for the pathogenesis. Recent studies have indicated that increased proteolytic cathepsin D activity in cardiomyocytes results in16kDa prolactin fragments with anti-angiogenic and apoptotic properties, which may contribute to the development of PPCM. In support of these findings, lowering full-length prolactin production by bromocriptine therapy has been reported to prevent impairment of cardiac function.PPCM is associated with an increased co-existence of pre-eclampsia, however, a causal relationship has been disputed. We hypothesize that the pathophysiology of PPCM and pre-eclampsia share the same molecular pathway: increased activity of trophoblastic matrix metalloproteinases at the feto-maternal interface may aggravate proteolysis of full-length prolactin, and subsequently the formed 16kDa prolactin fragments may contribute to deterioration of PPCM and pre-eclampsia. Therefore, we argue that it may be worthwhile to explore wether prolactin inhibition is not only beneficial for PPCM patients, but also for the much more prevalent pre-eclamptic women.Prolactin fragmentation by trophoblastic matrix metalloproteinases as a possible contributor to peripartum cardiomyopathy and pre-eclampsiaAnne Q. Reuwer, Paul J.H.M. Reuwer, Joris A. van der Post, Maarten J. Cramer, John J.P. Kastelein, Marcel Th.B. Twickler10.1016/j.mehy.2009.08.029Medical Hypotheses 74, 2 (2010)2009-09-14Medical Hypotheses2009-09-14742S0306-9877(09)X0013-7348352http://www.medical-hypotheses.com/article/PIIS0306987709005763/abstract?rss=yesAbstract: The cutaneous hemangiomas of infancy or infantile hemangiomas are the most common benign tumor of childhood. They were formerly known as strawberry hemangiomas in reason of its typical appearance although uncommon morphologic variations can be found. Usually hemangiomas are harmless growths that are the result of proliferation of endothelial cells during early childhood. Involution of the lesion occurs at 12–18months and can last up to 7years. Occasionally, infantile hemangiomas suffer dramatic overgrowth causing esthetical damages, as well compromises to vital structures that requires prompt intervention. Propranolol, a beta-adrenergic receptor antagonist that was invented by Sir James Black in 1960s, appears to be an effective treatment for infantile hemangiomas and should now be used as a first-line treatment in hemangiomas when intervention is required. Keloids (that resembles crab claws) and hypertrophic scars are fibrous tissue outgrowths that result from a derailment in the normal wound-healing process. Systemic or intralesional propranolol may play a role in the amelioration of keloids and hypertrophic scars due to their potential to induce vasoconstriction of over proliferating tissues, triggering apoptosis of endothelial cells and also to their effect as modulator of inflammatory process during wound healing. In adding the propranolol to the melting pot of abnormal (or supra-normal) wound healing, we hypothesized that we can battle keloids with propranolol.About strawberry, crab claws, and the Sir James Black’s invention. Hypothesis: Can we battle keloids with propranolol?Charles Jean G. de Mesquita10.1016/j.mehy.2009.08.035Medical Hypotheses 74, 2 (2010)2009-09-16Medical Hypotheses2009-09-16742S0306-9877(09)X0013-7353359http://www.medical-hypotheses.com/article/PIIS0306987709005660/abstract?rss=yesAbstract: Antiangiogenesis therapy is one of the most promising approaches to cancer treatment. Its clinical success has come out but still too limited. Vascularization of tumor is a complex and heterogenous process. So far, it has been demonstrated that several additional mechanisms can provide the tumor with oxygen and nutrients. Moreover, it is now clear that vascularization of tumor does not necessarily depend on endothelial cells proliferation and sprouting of new capillaries. Vasculogenic mimicry (VM) as an alternative circulatory system, has been described in multiple malignant tumor types, and considered to be associated with a poor prognosis for the patient. VM serves as an adjunct to the existing vasculature system, thereby aiding tumor growth as well as contributing to the metastatic process. Moreover, hypoxia has been confirmed to promote some tumor cells to form vessel-like tubes in vitro and express genes associated with VM. Yet, the current antiangiogenesis strategies, which are directed mainly against the tumor endothelium and then cause hypoxia of tumor cells, have no effect on VM. Our central hypothesis is that when the endothelium-dependent vessels are inhibited by the effective angiogenesis inhibitors, the hypoxia of tumor cells caused by antiangiogenesis may increase VM compensatively which can replace the job of endothelium-dependent vessels to maintain the tumor blood supply and provide a convenient route of tumor metastasis. As a result, antiangiogenesis therapy might have the unintended effect of promoting tumor metastasis by increasing VM. Thus, treatment strategies that target the tumor microcirculation should not only target endothelium-dependent vessels, but also take VM into account in tumors presenting VM.Antiangiogenesis therapy might have the unintended effect of promoting tumor metastasis by increasing an alternative circulatory systemBo Qu, Long Guo, Jinlu Ma, Yi Lv10.1016/j.mehy.2009.08.020Medical Hypotheses 74, 2 (2010)2009-09-10Medical Hypotheses2009-09-10742S0306-9877(09)X0013-7360361http://www.medical-hypotheses.com/article/PIIS0306987709004940/abstract?rss=yesSummary: Rest tremor is one of the four main clinical features of Parkinson’s disease (PD), besides rigidity, bradykinesia and postural instability. While rigidity, bradykinesia and postural instability can be explained with changes in neurotransmitter concentrations and neuronal activity in basal ganglia, the pathogenesis of parkinsonian tremor is not fully understood. According to the leading hypothesis tremor is generated by neurons or groups of neurons in the basal ganglia which act as central oscillators and generate repetitive impulses to the muscles of the body parts involved. The exact morphological substrate for central oscillators and the mechanisms leading to their activation are still an object of debate. Peripheral neural structures exert modulatory influence on tremor amplitude, but not on tremor frequency.We hypothesise that rest tremor in PD is the result of two mechanisms: increased activity and increased synchronisation of central oscillators. We tested our hypothesis by demonstrating that the reduction in rest tremor amplitude is accompanied by increased variability of tremor frequency. The reduction of tremor amplitude is attributed to decreased activity and poor synchronisation of central oscillators in basal ganglia; the increased variability of tremor frequency is attributed to poor synchronisation of the central oscillators. In addition, we demonstrated that the recurrence of clinically visible rest tremor is accompanied by a reduction in tremor frequency variability. This reduction is attributed to increased synchronisation of central oscillators in basal ganglia.We argue that both mechanisms, increased activity of central oscillators and increased synchronisation of central oscillators, are equally important and we predict that tremor becomes clinically evident only when both mechanisms are active at the same time. In circumstances when one of the mechanisms is suppressed tremor amplitude becomes markedly reduced. On the one hand, if the number of active central oscillators is very low, the muscle-stimulating impulses are too weak to cause clinically evident tremor. On the other hand, if central oscillator synchronisation is poor, the impulses originating from different central oscillators are not in phase and thus cancel out, again leading to reduced stimulation of muscles and reduced tremor amplitude. Our hypothesis is supported by our measurements on patients with PD and by experimental data cited in the literature.The proposed two mechanisms could have clinical implications. New medical treatments, which would specifically target only one of the proposed mechanisms (oscillator activity or synchronisation), could be effective in reducing tremor amplitude and thus supplement established antiparkinsonian treatments.Tremor amplitude and tremor frequency variability in Parkinson’s disease is dependent on activity and synchronisation of central oscillators in basal gangliaAndrej Bartolić, Zvezdan Pirtošek, Janez Rozman, Samo Ribarič10.1016/j.mehy.2009.06.057Medical Hypotheses 74, 2 (2010)2009-08-05Medical Hypotheses2009-08-05742S0306-9877(09)X0013-7362365http://www.medical-hypotheses.com/article/PIIS0306987709004939/abstract?rss=yesSummary: The adaptive immune system, fine tuned through millions of years of vertebrate evolution, discriminates self from foreign antigens through the deletion of auto-reactive clones and/or tolerization to self antigens. In this system, commonly encountered antigens should be recognized as self while rarely encountered antigens such as microbial or cancer derived molecules should be recognized as foreign. Throughout evolutionary history, the availability of cryptic self-antigens for presentation was enhanced though immune processing of damaged tissues due to infections, parasites and trauma – in other words, the hardscrabble conditions that prevailed throughout the vast majority of our evolutionary past. In situations where chronic tissue injury is reduced there is an increase in the incidence of autoimmune disease. A unifying hypothesis is thereby provided to explain the major epidemiological trends in autoimmune diseases, namely, (1) an historic increase in incidence, (2) increase in the incidence with increasing latitude, (3) increase in the incidence with higher socioeconomic status.The hardscrabble hypothesis: A reduction in chronic tissue damage has increased the incidence of autoimmune diseaseChristopher Naugler, David M. Conrad10.1016/j.mehy.2009.07.004Medical Hypotheses 74, 2 (2010)2009-08-05Medical Hypotheses2009-08-05742S0306-9877(09)X0013-7366367http://www.medical-hypotheses.com/article/PIIS0306987709004915/abstract?rss=yesSummary: Giant cell tumor of bone (GCTB) is a benign locally aggressive bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. Surgical treatment of GCTB is associated with high morbidity, and local recurrence. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease. If the tumor reaches close to the articulating surface a subchondral bone graft can be performed without risking a higher recurrence rate. Mineral trioxide aggregate (MTA) has been widely used to repair various kinds of tooth perforations. MTA is a powder aggregate containing mineral oxides with a good biological action and may facilitate the regeneration of the periodontal ligament and formation of bone. MTA used was able to induce bone regeneration and had its action optimized. Study has showed that, in the presence of MTA, cells grow faster and produce more mineralized matrix gene expression in osteoblasts. We hypothesize that MTA may has anti-recurrence properties. For the clinical point of view, we can apply MTA in the GCTB to induce bone production, then to inhibit the recurrent of the cases. MTA may be the therapy of choice for primary as well as recurrent giant cell tumors of bone.Could MTA be a novel medicine on the recurrence therapy for GCTB?Han Qin, Jun Cai, Jun Fang, Hongzhi Xu, Yongqing Gong10.1016/j.mehy.2009.07.002Medical Hypotheses 74, 2 (2010)2009-08-05Medical Hypotheses2009-08-05742S0306-9877(09)X0013-7368369http://www.medical-hypotheses.com/article/PIIS0306987709003855/abstract?rss=yesSummary: Recent studies show that ingestion of flavanol-rich cocoa powder provokes increased endothelial production of nitric oxide - an effect likely mediated by epicatchin – and thus may have considerable potential for promoting vascular health. The Kuna Indians of Panama, who regularly consume large amounts of flavanol-rich cocoa, are virtually free of hypertension and stroke, even though they salt their food. Of potentially complementary merit is the cyanobacterium spirulina, which has been used as a food in certain cultures. Spirulina is exceptionally rich in phycocyanobilin (PCB), which recently has been shown to act as a potent inhibitor of NADPH oxidase; this effect likely rationalizes the broad range of anti-inflammatory, cytoprotective, and anti-atherosclerotic effects which orally administered spirulina has achieved in rodent studies. In light of the central pathogenic role which NADPH oxidase-derived oxidant stress plays in a vast range of disorders, spirulina or PCB-enriched spirulina extracts may have remarkable potential for preserving and restoring health. Joint administration of flavanol-rich cocoa powder and spirulina may have particular merit, inasmuch as cocoa can mask the somewhat disagreeable flavor and odor of spirulina, whereas the antioxidant impact of spirulina could be expected to amplify the bioactivity of the nitric oxide evoked by cocoa flavanols in inflamed endothelium. Moreover, there is reason to suspect that, by optimizing cerebrovascular perfusion while quelling cerebral oxidant stress, cocoa powder and spirulina could collaborate in prevention of senile dementia. Thus, food products featuring ample amounts of both high-flavanol cocoa powder and spirulina may have considerable potential for health promotion, and merit evaluation in rodent studies and clinical trials.Potential complementarity of high-flavanol cocoa powder and spirulina for health protectionMark F. McCarty, Jorge Barroso-Aranda, Francisco Contreras10.1016/j.mehy.2008.09.060Medical Hypotheses 74, 2 (2010)2009-07-06Medical Hypotheses2009-07-06742S0306-9877(09)X0013-7370373http://www.medical-hypotheses.com/article/PIIS0306987709003740/abstract?rss=yesSummary: Periodontitis significantly decreases survival in hemodialysed patients with end stage renal disease (ESRD). Periodontitis-related microorganisms spreading into the bloodstream are thought to impair blood rheological parameters – for example, increasing whole blood viscosity, aggregating blood elements, and decreasing blood flow – and thereby significantly accelerate systemic or local diseases, impairing survival. We discuss the ability of a prototypical pathogenic anaerobic polybacterial consortium to modulate and interfere with host immune responses and to enzymatically degrade host proteins, to bind to and cleave extracellular matrix proteins, to invade intercellularly as well as intracellularly, to promote vascular permeability, to disrupt polymorphonuclear leukocyte function, to cleave complement, and to degrade IgG heavy chains. To further elucidate these phenomena, studies involving detecting microorganism byproducts and monitoring blood rheological parameters are necessary.Mechanism of increased mortality in hemodialysed patients with periodontitisJiří Šedý, Edita Horká, René Foltán, Jana Špačková, Jana Dušková10.1016/j.mehy.2009.04.053Medical Hypotheses 74, 2 (2010)2009-06-25Medical Hypotheses2009-06-25742S0306-9877(09)X0013-7374376http://www.medical-hypotheses.com/article/PIIS0306987709006136/abstract?rss=yesSummary: This paper provides information on the evolution of the ‘epigenetics’ concept since Aristotle and draws attention to the importance of epigenetic implications for cancer epidemiology in the years to come. Clearly, to understand origins of the concept of epigenetics, it is worthwhile to consider historical arguments associated with evolution. Equally clearly, in the last half of the 20th century, great advances in the understanding of epigenetics and, more specifically, great advances in the understanding of epigenetics in cancer have been made. However, reaping the full benefits of epigenetics lies beyond the predominant experimental studies of today. In general, epigenetics opens many doors in the field of cancer, but it also adds another level of complex, inter-related, and multi-dimensional information to research, and to its interpretation. Overall, future cancer studies should consider, or at least be sensitive to, epigenetic effects and mechanisms. Moving the focus beyond ‘pristine’ inheritance via DNA alone, cancer epidemiology investigating epigenetic exposures such as environmental factors (exposure to heavy metals, air pollution, arsenic and other toxins), dietary patterns (starvation, famine, contamination), and lifestyle habits (smoking, level of physical activity, and BMI) in populations has the prospect to significantly benefit future cancer prevention and treatment schemes.Epigenetics: Origins and implications for cancer epidemiologyMelissa S. Nise, Puran Falaturi, Thomas C. Erren10.1016/j.mehy.2009.09.008Medical Hypotheses 74, 2 (2010)2009-10-09Medical Hypotheses2009-10-09742S0306-9877(09)X0013-7377382http://www.medical-hypotheses.com/article/PIIS0306987709004927/abstract?rss=yesSummary: Secondary to the confluence of rising health care costs and higher quality data on the effectiveness of various medical interventions, cost-effectiveness analyses are becoming increasingly common. In this paper, we aim to assess the strengths and limitations of these analyses such that their interpretation and implementation can be maximized.The strengths of cost effectiveness analyses rest on the ‘bang-for-the-buck’ information they provide; allowing considerations of costs to be tied with therapeutic effectiveness – thereby (1) assisting in the decision making process between competing interventions for a particular disease process; and (2) between therapies to be used and diseases to be addressed via rationing. The weaknesses include (1) outcomes which depend greatly upon the methodologies used thereby confounding comparisons across studies; and (2) outcomes which, if used as the primary foundation of decision making, often conflict with societal values and desires. Accordingly, great care is suggested in interpreting the results of these studies and implementing such results in therapeutic or rationing decision making.Philosophical concerns regarding cost-effectiveness analysesBradley K. Weiner10.1016/j.mehy.2009.07.003Medical Hypotheses 74, 2 (2010)2009-08-03Medical Hypotheses2009-08-03742S0306-9877(09)X0013-7383386http://www.medical-hypotheses.com/article/PIIS030698770900601X/abstract?rss=yesSummary: There is data to support the hypothesis that US healthcare reform will require systemic changes in their delivery system rather than a segment-by-segment approach to improving individual components such as administrative or pharmaceutical costs or illness-by-illness programs such as comparative effectiveness or disease management. Mathematically, personnel costs provide the largest potential for savings. These costs are reflected in utilization rates. However, when governments or insurers try to control utilization, shortages or dissatisfaction ensue. Therefore, reform should be structured to encourage individually initiated reductions in utilization.This can be facilitated by changing from employer-paid comprehensive group policies of variable coverage to a three-part, standardized, individually purchased, group policy with a targeted deductible and co-pays that provide disincentives to over-utilization and incentives (refunds on unused contributions) to reduce utilization. There will be a public health policy (maternal, infant, and immunizations) that will be very inexpensive and not subject to any disincentives, a catastrophic policy with a deductible and enhanced but diminishing co-pays, and a Health Savings Account that pre-positions funds to cover the deductible and co-pays.These changes will lead to a reduction in administrative costs. The excess capacity created will provide care for the currently uninsured. Savings will be refunded to individuals thereby generating taxes that can pay for needed subsidies. Reform can be inexpensive if it puts the mathematics before the politics.Inexpensive health care reform: The mathematics of medicineRoger A. Forsyth10.1016/j.mehy.2009.08.046Medical Hypotheses 74, 2 (2010)2010-02-01Medical Hypotheses2010-02-01742S0306-9877(09)X0013-7387388http://www.medical-hypotheses.com/article/PIIS0306987709006124/abstract?rss=yesAll newborns look alike: walk into a neonatal ward – and every baby looks like every other baby. In fact, to correctly identify them hospital authorities tag the babies – to avoid confusion or mistaken identity. Now come with me as I saunter through an old age home. The older the residents are, the more they look similar. Though my statement appears a bit odd, most geriatric individuals, especially as they reach 80s or 90s start looking very much like each other. Just flip through a few photographs of new born infants or of people over 90, you will be amazed.The face as an index in health and diseaseArunachalam Kumar, C. Jairaj Kumar10.1016/j.mehy.2009.09.007Medical Hypotheses 74, 2 (2010)2009-10-16Medical Hypotheses2009-10-16742S0306-9877(09)X0013-7Correspondence389390http://www.medical-hypotheses.com/article/PIIS0306987709006562/abstract?rss=yesThe fetus produces enzymes in human embryo implantation, including the pathogenesis of ectopic pregnancy , thus an embryo can implant elsewhere than the uterus, which called ectopic pregnancy, and over 95% of all ectopic pregnancies occur in the fallopian tube. Tough ectopic pregnancy can cause rupture and great tissue damage in its efforts to reach a sufficient supply of blood, there is still case report of women who have abdominal pregnancy, which is another type of ectopic pregnancy, given birth . That indicates embryogenesis and development could be normally in sites other than the uterus. Immunohistochemical characterizations have suggested that ectopic pregnancy represent abnormal implantation of a morphologically normal blastocyst, giving rise to immunologically normal and hormonally active trophoblast cells . In case of that, can we remove the displaced embryo to a safe place, the uterus, to have a safe pregnancy?Can ‘ectopic pregnancy’ become ‘normal pregnancy’?Jing Fu, Cao Wang, Lina Hu10.1016/j.mehy.2009.09.038Medical Hypotheses 74, 2 (2010)2009-10-19Medical Hypotheses2009-10-19742S0306-9877(09)X0013-7Correspondence390390http://www.medical-hypotheses.com/article/PIIS0306987709006331/abstract?rss=yesIt is well documented that acetaminophen can cross the blood–brain barrier (BBB) and exert the antipyretic and analgesic effects. However, acetaminophen is metabolized through the glutathione (GSH) pathway in the liver. Prolonged or overdose of acetaminophen administration would lead to the liver necrosis, and even increase the risk of liver failure. The neurons in the central nervous system (CNS) are very sensitive to hypoxia, and the oxidative stress has been recognized as an important etiology of neural degenerative diseases. The decreased GSH concentration in the CNS would result in the declined defense against the oxidative stress and promote the neuron loss. Thus, Sharpe has suggested that the GSH consuming effect of acetaminophen could reduce the plasma GSH concentration. Subsequently, the plasma-derived GSH supply to the CNS is reduced and the toxic effect of oxidative stress is amplified . But in the present correspondence, new evidence will be presented to challenge the hypothesis drawn by Sharpe .Acetaminophen and neural degeneration: Is there a possible link?Ming-Xiang Ye, Jin-Lian Li10.1016/j.mehy.2009.09.028Medical Hypotheses 74, 2 (2010)2009-10-08Medical Hypotheses2009-10-08742S0306-9877(09)X0013-7Correspondence390391http://www.medical-hypotheses.com/article/PIIS0306987709006288/abstract?rss=yesIt is well known that brain iron appears to be elevated in several neurodegenerative diseases and that biogenic magnetite may be related to diseases such as Alzheimer’s disease. It has recently been shown that the total concentration of magnetite is generally higher in the Alzheimer brain, in some cases as much as 15 times greater than the controls . In plaque core material, magnetite and/or maghemite was identified as the dominant iron compound . Up to 100 million single-domain ferromagnetic crystals per gram for most tissues in the human brain has been reported and magnetic properties data indicate the crystals are in clumps of between 50 and 100 particles . Second only to the liver, the brain contains the highest quantity of iron, approximately 60mg of non-heme iron .Is magnetite involved in the formation of neurodegenerative diseases?Fredrik C. Størmer, Carl Morten Motzfeldt Laane10.1016/j.mehy.2009.09.023Medical Hypotheses 74, 2 (2010)2009-10-12Medical Hypotheses2009-10-12742S0306-9877(09)X0013-7Correspondence391391http://www.medical-hypotheses.com/article/PIIS0306987709006100/abstract?rss=yesThe mechanical function of the mammalian (human) heart as a hemodynamic organ pumping blood to whole body is well understood and known. However with more research focusing in the intrinsic system of the heart it was found that the cardiac afferent neurological input to the brain not only facilitate homeostatic regulation but also influences cognitive processing . This means that the heart has other role in emotion, cognition and sensory perception. In fact the heart could be considered as a sense and motor organ (my hypothesis). New scientific discoveries are now providing evidences which indicate that the heart indeed plays a significant role in emotional experience, modulate perception and is involved in intuitive perception and intention . These new discoveries are mainly based upon the anatomical structures and functions of the nervous system of the heart-the intrinsic system-(little brain) . Recent studies have shown that the heart has an endogenous neural intrinsic system independent of central medulla in brain stem, that control the heart, this intrinsic system is composed of hierarchy of neurons afferent, efferent and interconnected neurons that interact to form loops of circuits within which information processing take place . It is also established that the heart contains an intrinsic nervous system that exhibit both short and long term memory functions. In addition to the distributed network of cardiac ganglia the human heart contains approximately 40,000 specialized sensory neurites involved in relaying afferent information to the brain. These sensory neurites are sensitive to a wide range of mechanical and biochemicals stimuli . It is also possible that the specialized ventricular striated muscles and the conductive system of the heart including the Purkenje fibres are sensitive to external stimuli sources of information, which related to the intrinsic neural system of the heart . Through well established afferent pathways the sensory information is sent to the brain stem via vagal and sympathetic pathway and there is heart–brain interaction .The neurons in the mammalian myocardium have perceptive sensory functions locally in the heart like sensory cortical neurons of the brainAmna AlFaki10.1016/j.mehy.2009.09.005Medical Hypotheses 74, 2 (2010)2009-11-02Medical Hypotheses2009-11-02742S0306-9877(09)X0013-7Correspondence391392http://www.medical-hypotheses.com/article/PIIS0306987709006021/abstract?rss=yesWhat common features have the patients who died by novel influenza A (H1N1) or are affected by serious disease by this emergent virus? Initially seems that healthy young people are frequently affected. And some of them have experienced haemorrhagic exudation in lungs, that evolve fastly to respiratory distress syndrome and death . Some cases in Africans and mediterranean people have evolved suddenly to death.Platelet dysfunction can be the hidden risk factor for death in new influenza A (H1N1)Juan Martínez Hernandez10.1016/j.mehy.2009.08.040Medical Hypotheses 74, 2 (2010)2009-09-16Medical Hypotheses2009-09-16742S0306-9877(09)X0013-7Correspondence392393http://www.medical-hypotheses.com/article/PIIS0306987709006008/abstract?rss=yesSir, In my 2008 article in Medical Hypotheses titled “A hypothesis for anti-nanobacteria effects of gallium with observations from treating kidney disease” (1), I showed that gallium nitrate had benefit in treating kidney pain, perhaps by anti-nanobacteria action. I reported that oral gallium nitrate (120mg gallium per day), mixed with large amounts of drinking water (1% gallium nitrate) was used to treat chronic, treatment-resistant kidney stone pain and urinary tract bleeding in a 110lb female nurse. On the third day of gallium mineral water treatment, her urine appeared snow white, thick (rope-like), basic and suggestive of a calcific crystalline nature. After release of the white urine, it returned to normal in color, viscosity and pH. Kidney pain was absent, and there was no further evidence of blood in the urine. There were no treatment side effects or sequela. Gallium re-treatment was necessary after one year of absence of pain. I briefly reviewed the nanobacteria literature and reported that gallium had anti-bacterial action to all iron-dependent bacteria, thus I hypothesized a gallium – anti-nanobacteria linkage.Is gallium nitrate an effective kidney stone, calcified uterine fibroid, atherosclerosis and cataract anti-nanobacteria treatment? A case history and hypothesisGeorge Eby10.1016/j.mehy.2009.08.039Medical Hypotheses 74, 2 (2010)2009-09-16Medical Hypotheses2009-09-16742S0306-9877(09)X0013-7Correspondence393394http://www.medical-hypotheses.com/article/PIIS0306987709006690/abstract?rss=yesIn a recent article, the authors hypothesized that statins may be a potent therapeutic benefit in osteoarthritis . We found their idea to be very interesting. They based their hypotheses on the facts that statins may also protect cartilage from proteoglycan and collagen loss by inhibiting matrix metalloproteinases (MMPs) secretion. However, we think the hypotheses may be more persuasive when additional evidences are provided as following,Comment on “The matrix metalloproteinases as pharmacological target in osteoarthritis: Statins may be of therapeutic benefit”Yu-Ping Liu, Guang-Rong Yu10.1016/j.mehy.2009.09.050Medical Hypotheses 74, 2 (2010)2009-10-21Medical Hypotheses2009-10-21742S0306-9877(09)X0013-7Correspondence394395http://www.medical-hypotheses.com/article/PIIS0306987709006628/abstract?rss=yesOsteoarthritis (OA) is one of the most common joint diseases affecting the elder. In the past, OA research focused mainly on alterations of cartilage, because cartilage degeneration was believed to be the most significant event in OA. More recently, an increasing line of evidence suggests that subchondral bone and cartilage health seem to be tightly associated in the progression of OA . Bone proliferation either in the subchondral area in the cortical envelope of bone just below cartilage, which is known as eburnation, or at the margins of the bone, which is known as osteophytes, is also a hallmark of OA . Thus, OA should be recognized a disease that involves the entire joint, not just cartilage. In the rabbit model of anterior cruciate ligament transection – induced OA, excessive subchondral bone turnover occurred early. This phenomenon is associated with decreased bone mineral density (BMD), mineralization, trabecular bone volume, and thickness, lower connectivity, and thinner subchondral bone plate . Moreover, evidence is now accumulating that certain types of OA might initially be a bone disease rather than a cartilage disease. Radin et al. early found the interesting result that stiffening of subchondral bone preceded cartilage loss in the rabbit model of OA . Similarly, evidence from the Dunkin-Hartley guinea pig model indicated that subchondral changes preceded the changes in the cartilage . The results of these studies support the speculation that subchondral bone may be the primary organ triggering OA, with the concept that bone stiffness from microtrabecular fractures and their subsequent healing could increase the stiffness of the subchondral bone, transmitting increased load to overlying cartilage and leading to secondary cartilage damage , which challenged the traditional idea that OA is a disease whose central pathologic feature is hyaline articular cartilage loss.Targeting both cartilage and subchondral bone might be an optimal strategy for osteoarthritis therapyKai Huang, Xiao-wen Zhang, Gou-ping Ma, Fu-hua Zhong, Chun Zhang10.1016/j.mehy.2009.09.043Medical Hypotheses 74, 2 (2010)2009-10-26Medical Hypotheses2009-10-26742S0306-9877(09)X0013-7Correspondence395395http://www.medical-hypotheses.com/article/PIIS0306987709005982/abstract?rss=yesWe have read with interest the article by Dias et al., recently published in Medical Hypotheses . The authors claimed that the lack of available clinical applications of psychiatric neuroimaging is due to the fact that schizophrenia is a syndrome and not a disease: “the syndrome has more than one dimension (e.g., cognitive, psychotic and negative) and each of them is related to abnormalities in specific neuronal networks”. However, despite this claim, the authors did not provide reliable neuroimaging evidence for putative “abnormalities in specific neural networks” underlying cognitive, psychotic and negative domains of schizophrenia. Nowadays, psychiatric neuroimaging is clinically useless not only in the psychiatric diagnosis but also in the assessment of specific psychopathological domains such as hallucinations, delusions or cognitive impairments. To address these domains, nowadays psychiatrists speak to the patients and do not look through the scanner. In line with what our clinical experience gets, the authors correctly stated that there is “no singular and reductionist pathway from the nosographic entity (schizophrenia) to its causes”. However, they should have better clarified that there are not even consistent neuroimaging correlates for each of the aforementioned domains of schizophrenia. Presumably in the light of the lack of such evidence the authors argued for the “inexistence of a singular and reductionist pathway from manifestation to its causes, much like in the case of influenza and several other diseases”. We partly agree with them as we feel the authors are misunderstanding the meaning of necessary and sufficient causality. A person must be infected with the orthomyxovirus before he can develop influenza (necessary but not sufficient). Orthomyxovirus cannot “vary from case to case, or from group of patients to group of patients” as it is the necessary cause to influenza. Conversely, there is no necessary condition towards the development of schizophrenia as “no biological alterations are pathognomonic of schizophrenia” . Dias et al. have cited a number of neuroimaging meta-analyses to support their hypotheses. Despite the lack of consistent findings to be used in clinical psychiatry, available imaging literature indicates that schizophrenia is associated with brain abnormalities, but association is not causality. Thus, the cited meta-analyses cannot be used to prove that schizophrenia is a brain disease. For example, there is similar convincing evidence in psychiatric research indicating a strong association between schizophrenia and social defeat , migration , childhood abuse , mentalizing impairment . The reasons for neglecting the latter (sufficient) causes of schizophrenia to focus only on the imaging (or genetic) ones are obscure but may have to do with the rise of genetic-biological paradigms in recent decades. Other reasons may extend to underground conceptual limitations of psychiatric imaging (for a review see ). These include epistemological limits such as negativism of the issue, excessive faith in technology, neuro-realistic, mechanistic or reductionistic approaches . Of interest to the current debate may be the so called “mereological fallacy”, namely, the attribution of a property of a whole incorrectly to one of its parts. Psychiatric neuroimaging tempts us to think that psychiatric phenomena such as schizophrenia are properties of brains rather than humans. However, psychopathological states and mental disorders as psychosis currently use criteria that rely only on psychological terms. These terms are defined normatively, as fully recognized by Dias et al.: “a psychiatric diagnosis is a statistical procedure”. Thus, concretely speaking, a brain scan can never serve a priori as the sole criteria for the diagnosis of schizophrenia. Neuroimaging investigations can be extremely useful to diagnose disorders that use neuroradiological criteria in their definition, or further elucidate physiology, as we have showed in our research experience. In this respect, neuroimaging has undoubtedly made great advances in the study of the brain. Conversely, to diagnose psychosis, one talks to one’s patients. To bring neuroimaging into diagnostic use, we can be tempted to ‘eliminate’ mental illness and to redefine schizophrenia using pure radiological criteria . However, this leads to a conceptual difficulty: it does not take an expert to recognize that someone is psychotic but how would one decide whether fMRI activations were abnormal in the absence of a person with disorder? This is the crux of the issue: for neuroimaging to have any validity, and to be anything more than basic neuroscience, requires psychiatry to study the person. Normal and abnormal themselves are normatively defined and are not properties of the brain .Comment on “Schizophrenia, brain disease and meta-analyses: Integrating the pieces and testing Fusar-Poli’s hypothesis”Paolo Fusar-Poli10.1016/j.mehy.2009.08.045Medical Hypotheses 74, 2 (2010)2009-10-05Medical Hypotheses2009-10-05742S0306-9877(09)X0013-7Correspondence395396http://www.medical-hypotheses.com/article/PIIS0306987709005751/abstract?rss=yesA novel chemotherapy to cancer has been presented in a recent paper in your journal . Briefly, cell cycle specific agents (CCSA) and cell cycle non-specific agents (CCNSA) are simultaneously entrapped in one carrier, micelle, and the micelle can integrate advantages of the micelle and drug combination. The approach is meaningful, but it seems that it is not comprehensive. Here, we propose that not only multi-anticancer drugs but also enzymes can be simultaneously encapsulated in either micelle or other carrier for the treatment of cancer. The anticancer drugs and enzymes can act on targeting tumor cells through completely different mechanisms and produce synergistic effects. The micelles or other carriers are used to provide a slow release of the entrapped antineoplastic drugs in the carriers into the circulation system through passive diffusion. On the other hand, high molecular anticancer enzymes-entrapped carriers serve as circulating bioreactors. The low molecular substrate (i.e., asparagine) can enter into the circulating bioreactors. Inside the circulating bioreactors, the enzymatic reaction can be completed and then the auxotrophic tumor cells are killed due to lack of some certain amino acid.Not only anticancer drugs but also enzymes can be encapsulated in either micelle or other carrier for the treatment of cancerQunyou Tan, Jingqing Zhang, Li Zhang10.1016/j.mehy.2009.08.028Medical Hypotheses 74, 2 (2010)2009-09-17Medical Hypotheses2009-09-17742S0306-9877(09)X0013-7Correspondence396397http://www.medical-hypotheses.com/article/PIIS0306987709005738/abstract?rss=yesIn a recent paper, Trbovic proposes that schizophrenia could in essence be a circadian rhythm sleep disorder, and that dysfunction of the suprachiasmatic nucleus (SCN) might be central to this disturbance. In support of this interesting hypothesis the author provides a plethora of good circumstantial arguments, but ignores the already existing literature on a more direct involvement of the SCN in the pathophysiology of schizophrenia.Schizophrenia, sleep disturbances and the suprachiasmatic nucleus: Reduced nitric oxide synthase may matterHans-Gert Bernstein, Arndt Heinemann, Johann Steiner, Bernhard Bogerts10.1016/j.mehy.2009.08.026Medical Hypotheses 74, 2 (2010)2009-09-10Medical Hypotheses2009-09-10742S0306-9877(09)X0013-7Correspondence397398http://www.medical-hypotheses.com/article/PIIS0306987709005593/abstract?rss=yesAfter the publication of the Stroke Prevention with Aggressive Reductions in Cholesterol Levels (SPARCL) trial (which found that, in patients without known coronary heart disease who had a recent stroke or transient ischemic attack, treatment with 80mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events), it was pointed out how difficult it could have been translating its results into clinical practice .Statin therapy in the secondary prevention of cerebrovascular events: Is it really beneficial in clinical practice?Luca Mascitelli, Francesca Pezzetta, Mark R. Goldstein10.1016/j.mehy.2009.08.010Medical Hypotheses 74, 2 (2010)2009-09-04Medical Hypotheses2009-09-04742S0306-9877(09)X0013-7Correspondence398398http://www.medical-hypotheses.com/article/PIIS0306987709004770/abstract?rss=yesIn recent correspondence, Dr. Burton suggested to make often “costly, hard-won data” available to other researchers, be it for creative reviews , or beyond. In this very regard, I wish to thank Dr. Burton for his comment, add a piece of own experience and complement my contribution with a relevant historical example.“Open data” and Hardy’s example of seminal correspondence 101 years ago: Publication practices revisitedThomas C. Erren10.1016/j.mehy.2009.06.043Medical Hypotheses 74, 2 (2010)2009-07-30Medical Hypotheses2009-07-30742S0306-9877(09)X0013-7Correspondence398399