Medical Hypotheses (MED HYPOTHESES )

Publisher: Elsevier


The purpose of Medical Hypotheses is to provide a forum for the presentation and criticism of ideas in medicine and the related biomedical sciences. Most biomedical journals will publish ideas only in papers which also report observations. As the best scientists have repeatedly emphasized, this gives a misleading impression of the process of discovery. The ideas usually come first and they determine what observations should and will be made. Although fully acknowledged in other sciences, this central role of ideas in scientific progress is only now beginning to be widely recognized in medicine. Ideas occur to many people not in a position to test them experimentally. Ideas frequently require much fuller exposition than is allowed in the discussion section of an experimental paper. Ideas should be open to comment by scientists who have not done experimental work in the field. Medical Hypotheses will publish ideas or criticisms of ideas from any person, irrespective of whether any experimental testing of the ideas has been performed by the writer. Medical Hypotheses will also publish letters which comment on articles in the journal. Medical Hypotheses is the only journal fully devoted to the publication of ideas in the biomedical sciences. The justification for its existence is discussed in the editorial printed at the beginning of the first issue (January-February, 1975). If you feel that the aims of Medical Hypotheses are important and worthwhile, please encourage your library to subscribe to it.

Impact factor 1.15

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    Medical Hypotheses website
  • Other titles
    Medical hypotheses
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  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

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  • Pre-print
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    • Pre-print allowed on any website or open access repository
    • Voluntary deposit by author of authors post-print allowed on authors' personal website, or institutions open scholarly website including Institutional Repository, without embargo, where there is not a policy or mandate
    • Deposit due to Funding Body, Institutional and Governmental policy or mandate only allowed where separate agreement between repository and the publisher exists.
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months .
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    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PubMed Central after 12 months
    • Publisher last contacted on 18/10/2013
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    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Sudden infant death syndrome (SIDS) is a major cause of infant mortality throughout the world, yet its cause and mechanism of action remain poorly understood. Here, we discuss a novel model of the etiology of SIDS which ties together what is known about the brain regions thought to be affected in SIDS infants with a defined neuroanatomical circuit and a documented preventative factor in young children. We propose that SIDS occurs due to a lack of sufficient development and plasticity of glutamatergic synapses in the mesencephalic nucleus of the trigeminal nerve (Me5) and reticular formation (RF) of the brainstem. This model is supported by evidence of brainstem dysfunction in SIDS as well as evidence of signaling through the Me5 and RF in another means of regulating cortical arousal. Furthermore, long-term plasticity of glutamatergic synapses is well known to play a critical role in learning and memory in other regions of the brain, implying that those mechanisms may also be relevant in the development of brainstem circuitry. This model clearly explains why SIDS deaths appear so suddenly with little pathological explanation and suggests a potentially novel way to prevent these deaths from occurring. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 01/2015; 84(1):8-10.
  • G. Ottaviano, G. Marioni, G. Frasson, D. Zuccarello, R. Marchese-Ragona, C. Staffieri, E. Nardello, A.C. Frigo, C. Foresta, A. Staffieri
    Medical Hypotheses 01/2015;
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    ABSTRACT: Tuberculosis is continuing as a problem of mankind. With evolution, MDR and XDR forms of tuberculosis have emerged from drug sensitive strain. MDR and XDR strains are resistant to most of the antibiotics, making the management more difficult. BCG vaccine is not providing complete protection against tuberculosis. Therefore new infections are spreading at a tremendous rate. At the present moment there is experimental evidence to believe that Vitamin A and Vitamin D has anti-mycobacterial property. It is in this context, we have hypothesized a host based approach using the above vitamins that can cause possible prevention and cure of tuberculosis with minimal chance of resistance or toxicity.
    Medical Hypotheses 01/2015;
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    ABSTRACT: Recent studies of Autism Spectrum Disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Decompressive craniectomy (DC) is a surgical procedure used to relieve severely increased intracranial pressure (ICP) by removing a portion of the skull. Following DC, the brain expands through the skull defect created by DC, resulting in transcalvarial herniation (TCH). Traditionally, people measure only changes in the ICP but not in the intracranial volume (ICV), which is equivalent to the volume of TCH (VTCH), in patients undergoing DC.
    Medical Hypotheses 12/2014;
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    ABSTRACT: "Bovine spongiform encephalopathy", "scrapie", as well as Creutzfeldt-Jakob disease and kuru belong to a group of related neurological conditions termed "transmissible spongiform encephalopathies". These diseases are based on the LD50 measurement whereby saline brain homogenates are injected into experimental animals and when 50% of them develop symptoms, this is considered as transmission of the disease, but the gold standard for diagnosis is autopsy examination. However, an untenable assumption is being made in that saline brain homogenates do not cause tissue damage but it is known since the time of Pasteur, that they give rise to "post-rabies vaccination allergic encephalomyelitis". This is the fundamental flaw in the diagnosis of these diseases. A way forward, however, is to examine infectious agents, such as Acinetobacter which show molecular mimicry with myelin and elevated levels of antibodies to this microbe are found in multiple sclerosis patients and animals affected by "bovine spongiform encephalopathy". Copyright © 2014. Published by Elsevier Ltd.
    Medical Hypotheses 12/2014;
  • Medical Hypotheses 12/2014;
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    ABSTRACT: The brachial artery flow-mediated dilation test (FMD) is the non-invasive gold-standard used to test endothelial function. Reduced FMD precedes the development of atherosclerosis and provides an early marker for predicting future cardiovascular disease events. Although, this test is of high potential, it is somewhat limited by poor reproducibility. By utilizing hand warming and grip exercise combined with hierarchical linear modeling, shear rate-diameter dose-response curves may provide a novel and more accurate way to assess endothelial function in humans. Shear rate-diameter dose-response curves could potentially improve upon the traditional FMD measurement and serve as a superior clinical and research tool for assessing cardiovascular disease risk in a variety of populations. The current paper presents testable hypotheses and methodology for assessing the validity and reliability of an alternative to the current FMD test. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Objective: Temporomandibular disorders (TMD) are an assorted set of clinical conditions characterized mainly by pain in the temporomandibular joint (TMJ). TMJ inflammation or synovitis is frequently observed in TMD patients and is the major reason for TMD pain. TMD is prevalent in women of childbearing age, at least twice than in men, implying that estrogen may be involved in TMD pain processing. Estrogen affects a cell mainly through the estrogen receptors (ER). The estrogen–ER complex binds to estrogen response element sequences (ERE) in the promoter region of specific genes and then exerts its regulatory potential. The voltage-gated sodium channel 1.7 (Nav1.7), whose single disruption leads to a complete loss of pain, amplifies weak stimuli in the neurons and acts as the threshold channel for firing action potentials and plays a prominent role in pain perception, including inflammatory pain. Furthermore, our previous study showed that trigeminal ganglionic Nav1.7 was involved in the hyperalgesia of the inflamed TMJ. We propose that estrogen may enhance hyperalgesia of inflamed TMJ through decrease nociceptive threshold of TMJ or inflamed TMJ by modulating both expression and channel threshold of Nav1.7 in trigeminal ganglion.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Repeated morphine administration usually leads to a number of neuroadaptive processes, including tolerance and sensitization. However, research has shown that the induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor (NMDAR) activation. Chronic morphine exposure has been shown to result in spinal sensitization and activation of spinal NMDARs. Chronic morphine treatment and the activation of spinal NMDARs may be synergistic and form a closed loop that may worsen the development of morphine analgesic tolerance and spinal sensitization. Inhibition of NMDARs with an antagonist could effectively alleviate the development of morphine analgesic tolerance. So, what is the effect of modulating spinal NMDAR activation with exogenous agonists or neuropathic input on the development of morphine-induced analgesic tolerance? Our hypothesis is that chronic morphine treatment may worsen the already activation of spinal NMDARs and spinal sensitization after agonist application or neuropathic input to shorten the process of morphine-induced analgesic tolerance. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Cigarette smoke contains numerous toxic, carcinogenic and mutagenic chemicals, stable and unstable free radicals and reactive oxygen species (ROS) which cause biological oxidative damage. Continuous exposure to those chemicals leads to immense amount of damage to the human health either directly or indirectly. A hypothesis is advanced here that a possible explanation for developing autoimmune hepatitis (AIH) is due to regular smoking for long years of time. To examine this hypothesis, I relied on an experience of a case of a patient, as well as critical reading of the literature on smoking and different autoimmune disorders. Among the autoimmune diseases, rheumatoid arthritis (RA), multiple sclerosis (MS), thyroid disease, primary biliary cirrhosis (PBC) are reported mostly among tobacco-exposed animals. The observational and theoretical knowledge strengthen the hypothesis that smoking can be one of the causes of generating autoimmune hepatitis. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches for changing the regular smoking behavior. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: The development of innovative anti-aging strategy is urgently needed to promote healthy aging and overcome the occurrence of age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases. Genomic instability, deregulated nutrient sensing and mitochondrial dysfunction are established hallmark of aging. Interestingly, the orphan nuclear receptors NR4A subfamily (NR4A1, NR4A2 and NR4A3) are nutrient sensors that trigger mitochondria biogenesis and improve intrinsic mitochondrial function. In addition, NR4A receptors are components of DNA repair machinery and promote DNA repair. Members of the NR4A subfamily should also be involved in anti-aging properties of hormesis since these receptors are induced by various form of cellular stress and stimulate protective cells response such as anti-oxidative activity and DNA repair. Previous studies reported that NR4A nuclear receptors subfamily is potential therapeutic targets for the treatment of age related disorders (e.g. metabolic syndromes, diabetes and neurodegenerative diseases). Consequently, we propose that targeting NR4A receptors might constitute a new approach to delay aging and the onset of diseases affecting our aging population. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Thiamine deficiency (TD) is accepted as the cause of beriberi because of its action in the metabolism of simple carbohydrates, mainly as the rate limiting cofactor for the dehydrogenases of pyruvate and alpha-ketoglutarate, both being critical to the action of the citric acid cycle. Transketolase, dependent on thiamine and magnesium, occurs twice in the oxidative pentose pathway, important in production of reducing equivalents. Thiamine is also a cofactor in the dehydrogenase complex in the degradation of the branched chain amino acids, leucine, isoleucine and valine. In spite of these well accepted facts, the overall clinical effects of TD are still poorly understood. Because of the discovery of 2-hydroxyacyl-CoA lyase (HACL1) as the first peroxisomal enzyme in mammals found to be dependent on thiamine pyrophosphate (TPP) and the ability of thiamine to bind with prion protein, these factors should improve our clinical approach to TD. HACL1 has two important roles in alpha oxidation, the degradation of phytanic acid and shortening of 2-hydroxy long-chain fatty acids so that they can be degraded further by beta oxidation. The downstream effects of a lack of efficiency in this enzyme would be expected to be critical in normal brain metabolism. Although TD has been shown experimentally to produce reversible damage to mitochondria and there are many other causes of mitochondrial dysfunction, finding TD as the potential biochemical lesion would help in differential diagnosis. Stresses imposed by infection, head injury or inoculation can initiate intermittent cerebellar ataxia in thiamine deficiency/dependency. Medication or vaccine reactions appear to be more easily initiated in the more intelligent individuals when asymptomatic marginal malnutrition exists. Erythrocyte transketolase testing has shown that thiamine deficiency is widespread. It is hypothesized that the massive consumption of empty calories, particularly those derived from carbohydrate and fat, results in a high calorie/thiamine ratio as a major cause of disease. Because mild to moderate TD results in pseudo hypoxia in the limbic system and brainstem, emotional and stress reflexes of the autonomic nervous system are stimulated and exaggerated, producing symptoms often diagnosed as psychosomatic disease. If the biochemical lesion is recognized at this stage, the symptoms are easily reversible. If not, and the malnutrition continues, neurodegeneration follows and results in a variety of chronic brain diseases. Results from acceptance of the hypothesis could be tested by performing erythrocyte transketolase tests to pick out those with TD and supplementing the affected individuals with the appropriate dietary supplements. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: It is known, that initial events in atherosclerosis arise in the intima with a parallel influx of inflammatory cells. I propose the opposite - that the disease onset begins from the media vascular smooth muscle cell (VSMC) involvement and through its utilization of modified low-density lipoproteins (LDL), and free or esterified cholesterol. Other oxidized lipoprotein molecules remain in the media which are non-removed by high-density lipoproteins (HDL), owing to their structural damages after local vasa vasorum and adventitia lymphatic disorders. Mechanism by which VSMC ingulf and degrade them includes lipid-driven activation of VSMC reverse cholesterol transport pathways from the media to macrophages, and from the last - to plasma HDL (non-damaged) and apoA-1 or - directly to them. When some of the pathways are impaired, its demands a reprogramming of the existing cholesterol removal route to another, or selective gene involvements and transcriptional regulation of inflammatory signaling. Intima cell call-effects may be linked after their down-regulation with the expression of cytokines, chemokines by migrating VSMC to stem cells for dose-dependant proliferation, VSMC and macrophage maturation in non- and inflammatory phases of early or late atherosclerosis. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in developed countries of the world, while the main cause of mortality and morbidity in COPD patients are acute exacerbations and cardiovascular diseases. With regard to the frequency of exacerbations the phenotype «frequent exacerbators» has been defined, which, besides a more severe clinical course and a significantly higher total mortality, is also characterised by an elevated risk of cardiovascular mortality, as some indicators show us. It is notable that during the exacerbation of COPD, next to other changes, a significant aggravation of endothelial function occurs while the ED and COPD relationship seems very complex and is still in greater part unknown. Making the pathophysiological link between the frequency of exacerbations of COPD and ED could change our understanding of the character of this type of pulmonary disease. We hypothesize that frequent exacerbator COPD is a progressive and generalised vascular disease, not only an isolated respiratory disorder with ancillary systemic effects. Our opinion is that differences in COPD phenotype do not only determine the clinical picture but could also be of key importance in defining the progressivity of the disease. ED, which in these patients persists between frequent exacerbations, could be the main cause of the progression of pulmonary disease, and not only of the high cardiovascular risk of these patients. Such a persistent ED in FE COPD, with its pro-inflammatory, vasoconstrictory and prothrombotic mechanisms, could contemporaneously induce new exacerbations of COPD, the progression of pulmonary changes and the development of systemic atherosclerosis as a main extrapulmonary manifestation in these patients. Such a model defines endothelium as a common soil of progressive pulmonary and cardiovascular changes in FE COPD. It can fully explain all the elements of the clinical course and co-morbidity in FE COPD, for which we still do not have adequate explanation. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 12/2014;
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    ABSTRACT: Ovulation is an important physiological process in human, and its effect may reflect in body fluids via secretion of biomolecules such as proteins, amino acids, antioxidants, antimicrobial peptides and so on. Recently, the non-invasive sampling approaches are used to diagnose disease status and access health condition of human. Saliva comprises various proteins which are secreted through salivary glands. The proteins present in the saliva may vary in their expression according to the hormonal level and physiological nature of the body which are said to be hormone receptors, stress proteins and antimicrobial peptides. Therefore, it is postulated that saliva can be used in the detection of ovulation time in human using specific protein(s) expression and which can be considered as a best non-invasive method. The identification of these proteins by adopting LC–MS/MS followed by Western blot analysis are possible to identify a promising biomarker for ovulation detection in human.
    Medical Hypotheses 12/2014;