Medical Hypotheses RSS feed: Current Issue. Medical Hypotheses is a forum for ideas in medicine and related biomedical sciences. It will publish interesting and important theoretical papers that foster the diversity and debate upon which the scientific process thrives. The Aims and Scope of Medical Hypotheses are no different now from what was proposed by the founder of the journal, the late Dr David Horrobin. In his introduction to the first issue of the Journal, he asks 'what sorts of papers will be published in Medical Hypotheses? and goes on to answer 'Medical Hypotheses will publish papers which describe theories, ideas which have a great deal of observational support and some hypotheses where experimental support is yet fragmentary'. (Horrobin DF, 1975 Ideas in Biomedical Science: Reasons for the foundation of Medical Hypotheses. Medical Hypotheses Volume 1, Issue 1, January-February 1975, Pages 1-2.). Medical Hypotheses was therefore launched, and still exists today, to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals. 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. Submitted manuscripts will be reviewed by the Editor and external reviewers to ensure their scientific merit. All reviewers will be fully aware of the Aims and Scope of the Journal and will be judging the premise, originality and plausibility of the hypotheses submitted. Abstracting/indexing Medical Hypotheses is indexed and abstracted in: ADONIS, BIOSIS, Chemical Abstracts, Elsevier BIOBASE/Current Contents/Life Sciences, EMBASE Excerpta Medica, Index Medicus, Medical Documentation Service, Reference Update, Research Alert, Science Citation Index, SciSearch UMI (Microfilm), Russian Academy of Science http://www.medical-hypotheses.com/?rss=yesElsevier Inc.en © 2012 Elsevier Ltd. All rights reserved. Medical Hypotheses0306-9877786June 2012 © 2012 Elsevier Ltd. All rights reserved. healthpermissions@elsevier.comhttp://www.medical-hypotheses.com/article/PIIS0306987712001776/abstract?rss=yesTitle page/Editorial Board10.1016/S0306-9877(12)00177-6Medical Hypotheses 78, 6 (2012)2012-06-01Medical Hypotheses2012-06-01786S0306-9877(12)X0005-7iihttp://www.medical-hypotheses.com/article/PIIS0306987712000783/abstract?rss=yesAbstract: It was previously hypothesized that dextromethorphan (DM) and dextrorphan (DX) may possess antidepressant properties, including rapid and conventional onsets of action and utility in treatment-refractory depression, based on pharmacodynamic similarities to ketamine. These similarities included sigma-1 (σ1) agonist and NMDA antagonist properties, calcium channel blockade, muscarinic binding, serotonin transporter (5HTT) inhibition, and μ receptor potentiation. Here, six specific hypotheses are developed in light of additional mechanisms and evidence. Comparable potencies to ketamine for DM and DX are detailed for σ1 (DX>DM>ketamine), NMDA PCP site (DX>ketamine>DM), and muscarinic (DX>ketamine>>>>DM) receptors, 5HTT (DM>DX≫ketamine), and NMDA antagonist potentiation of μ receptor stimulation (DM>ketamine). Rapid acting antidepressant properties of DM include NMDA high-affinity site, NMDR-2A, and functional NMDR-2B receptor antagonism, σ1 stimulation, putative mTOR activation (by σ1 stimulation, μ potentiation, and 5HTT inhibition), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ1 stimulation, μ potentiation, and 5HTT inhibition), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ1 and mTOR signaling. Those for dextrorphan include NMDA high-affinity site and NMDR-2A antagonism, σ1 stimulation, putative mTOR activation (by σ1 stimulation and ß adrenoreceptor stimulation), putative AMPA receptor trafficking (by mTOR activation, PCP antagonism, σ1 stimulation, ß stimulation, and μ antagonism), and dendritogenesis, spinogenesis, synaptogenesis, and neuronal survival by NMDA antagonism and σ1 and mTOR signaling. Conventional antidepressant properties for dextromethorphan and dextrorphan include 5HTT and norepinephrine transporter inhibition, σ1 stimulation, NMDA and PCP antagonism, and possible serotonin 5HT1b/d receptor stimulation. Additional properties for dextromethorphan include possible presynaptic α2 adrenoreceptor antagonism or postsynaptic α2 stimulation and, for dextrorphan, ß stimulation and possible muscarinic and μ antagonism. Treatment-refractory depression properties include increased serotonin and norepinephrine availability, PCP, NMDR-2B, presynaptic alpha-2 antagonism, and the multiplicity of other antidepressant receptor mechanisms. Suggestions for clinical trials are provided for oral high-dose dextromethorphan and Nuedexta (dextromethorphan combined with quinidine to block metabolism to dextrorphan, thereby increasing dextromethorphan plasma concentrations). Suggestions include exclusionary criteria, oral dosing, observation periods, dose–response approaches, and safety and tolerability are considered. Although oral dextromethorphan may be somewhat more likely to show efficacy through complementary antidepressant mechanisms of dextrorphan, a clinical trial will be more logistically complex than one of Nuedexta due to high doses and plasma level variability. Clinical trials may increase our therapeutic armamentarium and our pharmacological understanding of treatment-refractory depression and antidepressant onset of action.An extension of hypotheses regarding rapid-acting, treatment-refractory, and conventional antidepressant activity of dextromethorphan and dextrorphanEdward C. Lauterbach10.1016/j.mehy.2012.02.012Medical Hypotheses 78, 6 (2012)2012-03-09Medical Hypotheses2012-03-09786S0306-9877(12)X0005-7Articles693702http://www.medical-hypotheses.com/article/PIIS0306987712000795/abstract?rss=yesAbstract: Acute coronary syndrome, including myocardial infarction, can occur as a result of ischaemia–reperfusion injury caused by acute occlusion of the coronary vessel/s following the rupture of an atherosclerotic plaque. Superimposed thrombosis at the lesion obstructs blood supply to the myocardium causing myocardial necrosis and ischaemic inflammation. Although not fully described, researchers believe that this process is initiated by a dysfunctional endothelium that activates the nearby leukocytes in the blood stream, thus attracting them to the arterial wall and initiating a cascade of complex mechanisms that lead to myocardial infarction. Interestingly, this process is two sided as the leaking soluble factors from a damaged and/or necrotic myocardium enter the systemic circulation, activating the innate and adaptive cell-mediated immune responses, which include increasing cytotoxic mediators. We hypothesize that this unwanted side effect of increase in proinflammatory mediators can lead to harmful systemic immune reactions directed towards various dysfunctional endothelia. Additionally, a strong inflammatory response, caused by myocardial damage, can impair ventricular function, on top of baseline necrosis. To evaluate this hypothesis, we propose to use in vivo tests to measure endothelial dysfunction, as well as ventricular dysfunction by ultrasound methods, and their correlation with immunological and/or biochemical parameters. These tests will be useful in assessing the risk and therapeutic outcome in patients with acute coronary syndrome.Harmful immune reactions during acute myocardial infarctionG. Laskarin, L. Zaputovic, V. Persic, A. Ruzic, V. Sotosek Tokmadzic10.1016/j.mehy.2012.02.013Medical Hypotheses 78, 6 (2012)2012-03-09Medical Hypotheses2012-03-09786S0306-9877(12)X0005-7Articles703706http://www.medical-hypotheses.com/article/PIIS0306987712000813/abstract?rss=yesAbstract: The pathogenesis of multiple sclerosis (MS), a disease characterized by demyelination and subsequent axonal degeneration, is as yet unknown. Also, the nature of the disease is as yet not established, since doubts have been cast on its autoimmune origin. Genetic and environmental factors have been implied in MS, leading to the idea of an overall multifactorial origin. An unexpected role in energizing the axon has been reported for myelin, supposed to be the site of consumption of most of oxygen in brain. Myelin would be able to perform oxidative phosphorylation to supply the axons with ATP, thanks to the expression therein of mitochondrial FoF1-ATP synthase, and respiratory chains. Interestingly, myelin expresses the pathway of heme synthesis, hence of cytochromes, that rely on heme group, in turn depending on Fe availability. Poisoning by these pollutants shares the common characteristic to bring about demyelination both in animal models and in man. Carbon monoxide (CO) and lead poisoning which cause functional imbalance of the heme group, as well as of heme synthesis, cause myelin damage. On the other hand, a lack of essential metals such as iron and copper, produces dramatic myelin decrease. Myelin is a primary target, of iron shortage, indicating that in myelin Fe-dependent processes are more active than in other tissues. The predominant spread of MS in industrialized countries where pollution by heavy metals, and CO poisoning is widespread, suggests a relationship among toxic action of metal pollutants and MS.According to the present hypothesis, MS can be primarily triggered by environmental factors acting on a genetic susceptibility, while the immune response may be a consequence of a primary oxidative damage due to reactive oxygen species produced consequently to an imbalance of cytochromes and respiratory chains in the sheath.Impairment of heme synthesis in myelin as potential trigger of multiple sclerosisAlessandro Morelli, Silvia Ravera, Daniela Calzia, Isabella Panfoli10.1016/j.mehy.2012.02.015Medical Hypotheses 78, 6 (2012)2012-03-09Medical Hypotheses2012-03-09786S0306-9877(12)X0005-7Articles707710http://www.medical-hypotheses.com/article/PIIS0306987712000825/abstract?rss=yesAbstract: People with abnormal breast tissue can eventually present breast cancer symptoms. The aim of this paper is to examine new prognostic methods for breast cancer using electroencephalographic techniques (EEG). Since it is known that electrical brain activity can be recorded by EEG, and since proteins and genes affect the electrical activity of the brain via the control of the flow of Na+ and K+ ions, and also given the fact that breast cancer and many other types of cancer are associated with 14-3-3 protein and genes, we hypothesize that there is a relationship between breast cancer and EEG. We examine the theoretical linkages between EEG, genes and proteins, and breast cancer, and propose the development of an intelligent technique for associating EEG with the early stages of breast cancer (i.e., atypical hyperplasia) as a fingerprint characteristic. This novel approach may provide the means for a new diagnostic and prognostic approach to early stage breast cancer, and other cancers.Is it possible to extract a fingerprint for early breast cancer via EEG analysis?Marios Poulos, Theodoros Felekis, Angelos Evangelou10.1016/j.mehy.2012.02.016Medical Hypotheses 78, 6 (2012)2012-03-14Medical Hypotheses2012-03-14786S0306-9877(12)X0005-7Articles711716http://www.medical-hypotheses.com/article/PIIS0306987712000837/abstract?rss=yesAbstract: Patients with familial Mediterranean fever (FMF) have a susceptibility to the development of multiple sclerosis (MS). Here, we will propose the possible underlying pathophysiological mechanisms of this predisposition. Inflammation, disruption of blood–brain barrier (BBB), mitochondrial energy deficit, demyelination, and axonal damage, which play an important role in the pathogenesis of MS, may occur during the course of FMF. Most FMF patients have homozygous mutations in the MEFV gene that codes for the protein pyrin. Also, pyrin mutations were found about 3.5 times higher in the MS patients than the healthy control group. Pyrin is implicated in the maturation and secretion of the proinflammatory cytokine IL-1β. IL-1β is a major mediator of fever and systemic inflammation, and mononuclear cells from FMF patients release higher levels of IL-1β. Moreover, IL-1 plays a significant role in the regulation of the T-cells, and it is considered an essential cytokine for the Th cell differentiation that implicated in the MS pathogenesis. In addition, endothelial dysfunction and vasculitis in FMF may cause BBB breakdown that is the first step in the development of MS lesions. Apart from this, damage can occur in myelin and mitochondria proteins due to high body temperature that arises during the FMF attacks. Whereas the protein damage in myelin results in demyelination, and the protein damage in mitochondria causes lack of energy. Both situations play a part in the pathogenesis of MS. Due to mitochondrial energy deficit, remyelination may not be achieved, and therefore, axonal damage increases. Thus, at the end of these pathophysiological processes, MS findings may occur in the FMF patients especially with irregular use of colchicine.The possible underlying pathophysiological mechanisms for development of multiple sclerosis in familial Mediterranean feverMahmut Alpayci, Nazim Bozan, Seyfettin Erdem, Muslum Gunes, Metin Erden10.1016/j.mehy.2012.02.017Medical Hypotheses 78, 6 (2012)2012-03-14Medical Hypotheses2012-03-14786S0306-9877(12)X0005-7Articles717720http://www.medical-hypotheses.com/article/PIIS0306987712000849/abstract?rss=yesAbstract: Inflammation integrates diverse mechanisms that are associated not only with pathological conditions, such as cardiovascular diseases, type 2 diabetes, obesity, neurodegenerative diseases and cancer, but also with physiological processes like reproduction i.e. oogenesis and embryogenesis as well as aging. In the current review we firstly propose that the inflammatory response could recapitulate the phylogenia. In this way, highly conserved inflammatory mechanisms that play a main role in the evolutive development of different animal species, both invertebrates as well as vertebrates, are identified. Therefore, we also hypothesize that inflammation could represent a key tool used by nature to modulate organisms according to the environmental conditions in which these develop. Thus, inflammation could be the pathway by which the environmental factors could be related to the evolutionary development. If so, the diverse human chronic inflammatory diseases that nowadays the Western society suffer would represent the way for adapting to the abrupt changes in their lifestyle. Nonetheless, the distribution of the different pathological conditions varies in terms of intensity and magnitude among Western country populations depending on their genetic polymorphism. In this case, it should be considered that this set of diseases, distributed between all the individuals that constitute the Westernized society, would represent a true Social Inflammatory Syndrome whose final result is its remodeling. In this context, the use of inflammation by the Western society could represent the camouflaged expression of efficient mechanisms of evolution and development. In addition, if the different types of the inflammatory response involved in these diverse chronic pathological conditions could trace the biochemical origins of life, perhaps inflammation could represent an archaeological tool of unsuspected usefulness for understanding our own origin.Coupling inflammation with evo-devoMaría-Angeles Aller, Natalia Arias, Sherezade Fuentes-Julian, Alejandro Blazquez-Martinez, Salvador Argudo, Maria-Paz de Miguel, Jorge-Luis Arias, Jaime Arias10.1016/j.mehy.2012.02.018Medical Hypotheses 78, 6 (2012)2012-03-14Medical Hypotheses2012-03-14786S0306-9877(12)X0005-7Articles721731http://www.medical-hypotheses.com/article/PIIS0306987712000850/abstract?rss=yesAbstract: A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close to the number of patients suffering from the disease. This hypothesis is based on a study of bipolar disorder.Genetics of complex diseases: Variations on a themeErling Mellerup, Gert Lykke Møller, Pernille Koefoed10.1016/j.mehy.2012.02.019Medical Hypotheses 78, 6 (2012)2012-03-19Medical Hypotheses2012-03-19786S0306-9877(12)X0005-7Articles732734http://www.medical-hypotheses.com/article/PIIS0306987712000862/abstract?rss=yesAbstract: Infantile spasms (IS) are an age-specific epileptic syndrome associated with diverse etiological factors. In recent years, several hypotheses and animal models have been proposed to explain the pathogenesis of IS, but none has elucidated the pathophysiology of IS. In the current case-control study, prenatal stress degree was identified to be higher among the mothers of IS patients than those among the control group. The onset risk of IS increased with the degree of prenatal stress within a certain range. We have recently exposed pregnant rats to forced cold swimming and have given intraperitoneal injection of N-methyl-d-aspartate (NMDA) to rat pups with prenatal stress exposure. Prenatal stress exposure was found to alter the hormonal levels and neurotransmitter receptor expression of developing rats, sensitizing rat pups to develop NMDA-induced spasms and rendering the spasms to be sensitive to adrenocorticotropic hormone therapy. The studies above indicate that prenatal stress plays an important role in the onset of IS. Based on previous hypotheses and the current findings, we propose a prenatal stress exposure hypothesis for IS (also called Zou’s hypothesis).Prenatal stress exposure hypothesis for infantile spasmsXiu-yu Shi, Li-Ping Zou, Guang Yang, Ying-Xue Ding10.1016/j.mehy.2012.02.020Medical Hypotheses 78, 6 (2012)2012-03-19Medical Hypotheses2012-03-19786S0306-9877(12)X0005-7Articles735737http://www.medical-hypotheses.com/article/PIIS0306987712000874/abstract?rss=yesAbstract: We propose that the growth of solid tumors is dependent, in part, on the entry of large molecular blood-borne growth regulators into the tissue and is facilitated by the highly permeable nature of tumor blood vessels. There is abundant evidence that the tumor vasculature is hyperpermeable and tumor growth is dependent on mediators that increase vascular permeability (e.g., VEGF and mast cells). Therefore, the extravasation of plasma proteins into the interstitial space could be an important determinant of tumor growth. Angiogenesis promotes cancer by creating a network of blood vessels that supplies oxygen and nutriment. A highly permeable vasculature could complement this by facilitating the entry of plasma proteins into the tumor space, permitting them to exert effects on growth and survival pathways. Plasma proteins could act directly (on the cancer cells) or indirectly (via the stroma), and could conceivably stimulate cell proliferation, enhance cell survival, promote angiogenesis, and/or provide the cells with essential nutrients. Since increased vascular permeability is a hallmark of inflammation and since chronic inflammation is a forerunner to cancer, we also suggest that the prolonged influx of plasma proteins during chronic inflammation could contribute to the carcinogenic process. Perhaps over time and in sufficient quantity, the extruded plasma proteins and the attendant edema set up a feed-forward cycle that exacerbates the inflammation and potentiates the formation of mutagens and growth regulators. It is tempting to speculate that differences in tumor growth/metastasis and patient outcome are at least partly due to the degree of permeability of the tumor vasculature.Enhanced vascular permeability is hypothesized to promote inflammation-induced carcinogenesis and tumor development via extravasation of large molecular proteins into the tissueRobert E. Carraway, David E. Cochrane10.1016/j.mehy.2012.02.021Medical Hypotheses 78, 6 (2012)2012-03-30Medical Hypotheses2012-03-30786S0306-9877(12)X0005-7Articles738743http://www.medical-hypotheses.com/article/PIIS0306987712000886/abstract?rss=yesAbstract: Placebo effects spark more and more interest in both medicine and psychotherapy. Neurobiological findings have helped to understand underlying biochemical and neurological mechanisms although many questions remain to be answered. One common denominator of empirical findings regarding placebo effects across a wide range of clinical conditions (e.g., depression, Parkinson’s disease, pain, neurological disorders) is the involvement of higher cognitive brain functions associated with the prefrontal cortex. It is meanwhile commonly accepted that placebo effects involve self-regulatory mechanisms whose role in mediating those effects have not been thoroughly investigated yet. We propose a theoretical framework which helps to identify relevant functional mechanisms. Drawing on psychological findings, we propose a mechanism by which placebo effects can be maximized in any type of medical and psychotherapeutic setting.Placebo forte: Ways to maximize unspecific treatment effectsRainer Schneider, Julius Kuhl10.1016/j.mehy.2012.02.022Medical Hypotheses 78, 6 (2012)2012-03-26Medical Hypotheses2012-03-26786S0306-9877(12)X0005-7Articles744751http://www.medical-hypotheses.com/article/PIIS0306987712000898/abstract?rss=yesAbstract: Background: Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).Methods: This paper reviews the evidence that such symptoms are organically based. We use the term “physio-somatic” to describe these symptoms.Results: Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations.Conclusions: The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated “pathway phenotype”. These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations.Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue SyndromeGeorge Anderson, Michael Maes, Michael Berk10.1016/j.mehy.2012.02.023Medical Hypotheses 78, 6 (2012)2012-03-26Medical Hypotheses2012-03-26786S0306-9877(12)X0005-7Articles752756http://www.medical-hypotheses.com/article/PIIS0306987712000904/abstract?rss=yesAbstract: Charged by the Pope Julius II for painting the Cappella Sistina in Rome (between 1508 and 1512), Michelangelo worked in an elevated scaffolding, in an anomalous position with dyes (including poisoning lead salts) and solvents (such as toxic turpentine) dripping on his face and continuously inhaling, in a dim environment illuminated only with oil lamps and candles, as he described himself and sketched in a sonet addressed to Giovanni da Pistoia. In 1510 he began suffering from eye disease: the main symptom was the necessity to elevate the document he was reading up to the level of his eyes. This defect disappeared few months after he finished painting his masterpiece. We hypothesize that the Michelangelo’s eyes disease was a form of acquired and transitory nystagmus induced by the many hours he spent in up gaze, with a skew deviation, a form of ocular tilt reaction resulting from the impairment of spatial sensitivity (inversion illusion) due to the persistence of the artist’s head in a horizontal position, looking upward.Michelangelo’s eye diseaseP.E. Gallenga, Giampiero Neri, Ruggero D’Anastasio, Vito Enrico Pettorrossi, Emilio Alfieri, Luigi Capasso10.1016/j.mehy.2012.02.024Medical Hypotheses 78, 6 (2012)2012-03-16Medical Hypotheses2012-03-16786S0306-9877(12)X0005-7Articles757759http://www.medical-hypotheses.com/article/PIIS0306987712000916/abstract?rss=yesAbstract: A number of preclinical and clinical studies indicate multiple types of interaction between ethanol intake and the mood-related neurotransmitter, norepinephrine (NE). For example, ethanol interacts with dopamine beta-hydroxylase (DBH), an enzyme that plays an essential role in the only well-established endogenous synthetic pathway for NE, whereby dopamine is hydroxylated to form NE. While the DBH pathway may indeed be the only endogenous mechanism for producing NE, another possibility is that multiple means have evolved for the biosynthesis of this very important neurotransmitter, where some pathways may be independent of DBH. If so, such redundancy would provide greater assurance that enough NE is available for the body to use in this neurotransmitter’s various physiological roles. This paper puts forth the hypothesis ethanol is a substrate in a novel, endogenous synthetic pathway for NE, consistent with some studies showing that intake of ethanol increases the concentration of endogenous NE. Also consistent with this hypothesis, the molecular structure of ethanol is a physical subset of the structure of NE itself. If the hypothesis is correct, it may have important implications for understanding the physiological basis of alcohol use, abuse, and dependence in humans, as well as modeling these phenomena in animals. Importantly, the hypothesis is directly testable in rodents by presenting ethanol to DBH knockout mice, which are thought to lack NE, and then measuring if NE is synthesized in these animals.Neurodrinking: Is alcohol a substrate in a novel, endogenous synthetic pathway for norepinephrine?Paul J. Fitzgerald10.1016/j.mehy.2012.02.025Medical Hypotheses 78, 6 (2012)2012-03-16Medical Hypotheses2012-03-16786S0306-9877(12)X0005-7Articles760762http://www.medical-hypotheses.com/article/PIIS0306987712000928/abstract?rss=yesAbstract: Multiple sclerosis (MS) is an autoimmune neurological disorder. The role of ‘Acinetobacter’ has been examined using the method of Karl Popper and involves nine “Popper sequences”. (1) The frequency of MS increases with latitudes in the Northern Hemisphere, and the reverse is found in the Southern Hemisphere. (2) Sinusitis is found frequently at colder latitudes. (3) Sinusitis occurs frequently in patients with MS. (4) Specific sequences of bovine myelin when injected into experimental animals will produce a neurological disorder resembling MS which is called “experimental allergic encephalomyelitis”. (5) Computer analysis of myelin shows molecular mimicry with sequences found in Acinetobacter. (6) Antibodies to Acinetobacter bacteria are found in MS patients. (7) Acinetobacter bacteria are located on human skin and in the nasal sinuses. (8) IgA antibodies are preferentially elevated in the sera of MS patients, thereby suggesting the trigger microbe is acting across a mucosal surface probably located in the nasal sinuses. (9) Only Acinetobacter bacteria and no other microbes evoke statistically significant titres of antibodies in MS patients. These nine Popper sequences suggest that MS is most probably caused by infections with Acinetobacter bacteria in the nasal sinuses, and this could have therapeutic implications.The role of Acinetobacter in the pathogenesis of multiple sclerosis examined by using Popper sequencesAlan Ebringer, Taha Rashid, Clyde Wilson10.1016/j.mehy.2012.02.026Medical Hypotheses 78, 6 (2012)2012-04-09Medical Hypotheses2012-04-09786S0306-9877(12)X0005-7Articles763769http://www.medical-hypotheses.com/article/PIIS0306987712001089/abstract?rss=yesAbstract: The GPR-II model describes a “7-step” panic model. In this model, the single panic patient is not only affected as single member. The pressure weighing on him is not only exerted by external factors but also by group members of his network. Therefore, he has to cope with his individual problems and with the expectations of all members.The “therapeutic” model of instant sedation used (rescue screens) and long-lasting steps (behavioural therapy in group models) are not appropriate to treat the patients successfully.Global panic reaction II – A 7-step repetitive vicious circleW. Sperling, H. Müller10.1016/j.mehy.2012.03.001Medical Hypotheses 78, 6 (2012)2012-04-09Medical Hypotheses2012-04-09786S0306-9877(12)X0005-7Articles770771http://www.medical-hypotheses.com/article/PIIS0306987712001090/abstract?rss=yesSummary: The hypothesis proposed is that anorexia nervosa (AN) is an autoimmune disease caused by delayed exposure to common micro-organisms in which auto-antibodies to regulatory peptides and hypothalamic neurons, which cross react with microbial antigens, disturb appetite and lead to decreased intake of food. IgG, IgA and IgM auto-antibodies to a range of regulatory peptides concerned with appetite and mood are found in patients with AN. The regulatory peptides show sequence homology with common micro-organisms of the microbial flora. Auto-antibodies to α melanocyte stimulating hormone (αMSH) are positively correlated with AN psychopathology. But patients with bulimia nervosa (BN) and normal healthy controls also have a similar range of auto-antibodies at comparable levels. The incidence of AN is rising in developed countries, the disease is more common in females than in males, the peak incidence is in the teenage years, there is seasonal variation in the month of birth and the disease is more common in higher socio-economic groups. These are all features which are consistent with the hygiene hypothesis. But there is no evidence that the disease is more common in first born than in later born children. There is a paucity of data on early life events such as attendance at nursery and exposure to pets. Genetic factors are important but the data on major histocompatibility complex (MHC) gene polymorphisms are contradictory. The epidemiological and serological data are consistent with the hypothesis under investigation but key questions in relation to the hygiene hypothesis have not been posed. A large case control study of AN epidemiology is indicated. MHC gene polymorphisms should be assessed. There is, however, sufficient evidence to justify a trial of pooled immunoglobulin therapy in patients with life threatening AN.Anorexia nervosa, autoimmunity and the hygiene hypothesisMeghan J. Acres, Joseph J. Heath, James A. Morris10.1016/j.mehy.2012.03.002Medical Hypotheses 78, 6 (2012)2012-04-05Medical Hypotheses2012-04-05786S0306-9877(12)X0005-7Articles772775http://www.medical-hypotheses.com/article/PIIS0306987712001107/abstract?rss=yesAbstract: The incidence of a number of Th1 and Th2 diseases differs across populations. Interleukin-4 (IL-4) is a dispensable cytokine for the development of a type 2 immune response. Studies in which serum IL-4 levels were quantified in a healthy control group from some European and Asian countries propose that serum IL-4 levels may be higher in Asian compared to European countries. A simultaneous measurement of serum IL-4 levels in healthy individuals from different populations in a reference lab is needed to confirm different IL-4 levels across populations. If so, increased IL-4 levels might be an explanation for dissimilar incidence of some Th1 and Th2 diseases in different courtiers.Possible different serum IL-4 levels across populations: A reason for dissimilar incidence of Th1 and Th2 diseasesZahra Mojtahedi10.1016/j.mehy.2012.03.003Medical Hypotheses 78, 6 (2012)2012-03-30Medical Hypotheses2012-03-30786S0306-9877(12)X0005-7Articles776777http://www.medical-hypotheses.com/article/PIIS0306987712001120/abstract?rss=yesAbstract: Myopia is a common ocular disease in the world. Its prevalence has increased rapidly worldwide, especially in some East-Asian countries. Genetic factors and environmental factors both affect myopia’s onset and its progress. Iris colour is an important characteristic of a person. It is a possible risk factor for myopia by affecting the amount and the colour of light entering eyes. The study of iris colour may contribute to the understanding of myopia mechanism and provide good suggestive evidence for studies on other eye diseases. In this article, the possible connection between myopia and iris colour is proposed. Approaches to dissect any link are suggested.Myopia and iris colour: A possible connection?Weihua Meng, Jacqueline Butterworth, Patrick Calvas, Francois Malecaze10.1016/j.mehy.2012.03.005Medical Hypotheses 78, 6 (2012)2012-04-05Medical Hypotheses2012-04-05786S0306-9877(12)X0005-7Articles778780http://www.medical-hypotheses.com/article/PIIS0306987712001132/abstract?rss=yesAbstract: There are doubtful points about the theory that autoimmunity with auto-antibody (Ab) to TSH receptor (R) causes hyperthyroidism in Graves’ disease (GD). A main doubtful point is no curative effect of corticosteroid on Graves’ hyperthyroidism in spite of curative effect of corticosteroid for all autoimmune diseases. Recently we demonstrated the immunological similarity of TSAb and TBAb-IgG to animal IgGs, except for human (h)IgG, by neutralization and purification of TSAb and TBAb-IgG using (1) heterophilic Ab to animal IgG in GD sera and (2) experimentally generated anti-animal IgG Abs [such as dog (d), bovine (b), porcine (p), and rabbit (rb)]. Furthermore, greater immunological similarity of Fab- and F(ab′)2-portion of TSAb- and TBAb-IgG to bovine Fab, compared to hFab, was demonstrated using goat anti-bovine F(ab′)2 Ab.Existence of b and p TSH-like portions in the LATS-IgG molecule (probably Fab portion) was suggested by a previous report of neutralization of LATS activity by anti-b- or anti-p-TSH Ab. We suggested the existence of a mammalian animal-TSH-like structure, excepting hTSH, in the TSAb-IgG molecule (probably Fab portion), by discovery of anti-mammalian TSH Ab (such as d, b, p, guinea-pig, rat, whale, except h) in sera of GD. Lately, similar TSHR binding of H- and L-chain of human stimulating monoclonal TSHR Ab (M22)-Fab with TSH-α and-β subunit was reported. This evidence suggests that Fab portion of TSAb has a structure like mammalian TSH, but not hTSH.IgG-λ type of d, horse, b, p, goat, ovine is 95% and IgG-κ type is 5%, while human κ and λ chain is 60:40. Previous report that LATS (TSAb)-IgG composed of predominant λ type is supporting evidence that TRAb-IgG has immunological similarity with these animal IgGs compared to hIgG.We speculate that TSAb-IgG may be referred as a mermaid consisted in face (Fab) and trunk-leg (Fc). Face may be a kind of hormone with animal TSH-like structure and trunk-leg has animal IgG-like structure (in spite of no antibody function).There are many reports for co-existence of TSAb and TBAb-IgG in sera of GD. We reported conversion from TBAb (non-thyroid stimulating type IgG) to TSAb by co-incubation of anti-hIgG Ab (containing anti-animal IgG Ab as a cross-reaction) with TBAb-bound porcine thyroid cells. Thus, we suggest that TBAb may be the precursor form of TSAb.A novel hypothesis for the etiology of Graves’ disease: TSAb may be thyroid stimulating animal IgG-like hormone and TBAb may be the precursor of TSAbYukio Ochi, Yoshihiro Kajita, Takashi Hachiya, Masaru Hamaoki10.1016/j.mehy.2012.03.006Medical Hypotheses 78, 6 (2012)2012-04-03Medical Hypotheses2012-04-03786S0306-9877(12)X0005-7Articles781786http://www.medical-hypotheses.com/article/PIIS0306987712001144/abstract?rss=yesAbstract: Currently, breast cancer represents the most common indication for mastectomy with negative influence on personal perception, sexuality and partnership. Since the introduction of breast implants, silicone, and saline breast implantation have become one of the most common procedures performed by plastic surgeons, not only for aesthetic reasons but also for reconstructive purposes. These women will ultimately be faced with the prospect of capsular contracture. This is especially true in patients receiving radiation therapy, where irradiation increases the risk of complications, capsular contracture and may compromise a favorable aesthetic result. Despite the capsular contracture is the most common complication for both aesthetic and reconstructive breast surgery, the treatment have remained unsolved. Leukotriene antagonists (LTRAs) have emerged as effective prophylactic agents in the management of reactive airway diseases, and recently they have used as an off label prophylactic agent against the capsular contracture after breast augmentation. However up to now there is no any experimental research or clinical study in the medical literature about the effect of Zafirlukast on the capsular formation around irradiated silicone implants.The effect of Zafirlukast on capsule formation in post-radiation silicone implantsStamatis Sapountzis, Ji Hoon Kim, Daniela Francescato Veiga, Lydia Masako Ferreira10.1016/j.mehy.2012.03.007Medical Hypotheses 78, 6 (2012)2012-04-05Medical Hypotheses2012-04-05786S0306-9877(12)X0005-7Articles787789http://www.medical-hypotheses.com/article/PIIS0306987712001168/abstract?rss=yesAbstract: The oral epithelium together with the saliva and its components forms a complex structure which is the first line of defence in the oral cavity. The surface of superficial cells of the oral epithelium contains ridge-like folds, microplicae (MPL), which are typical of the surfaces of areas covered with protective mucus. The role of MPL seen on the upper surface of the oral epithelial cells is still unknown. The salivary mucus gel performs a protective diffusion membrane against harmful substances and this membrane is built up by epithelial cells covered by a highly hydrated and viscous gel, where mucins constitute the scaffold. The interaction between the MPL-structure and the mucins is shown in cornea, so that mucins are expressed on the tips of the MPL of the epithelial cells. We hypothesized that the MPL architecture of oral superficial epithelial cells provides the underlying basis for mucins’s protective function as well as in ocular surface. The salivary mucous barrier is required to protect the superficial cells and the MPL-structure together with membrane anchored mucin binding protein (MBP) forms the ground to this mucous barrier.So, oral mucosal barrier complex (OMBC) contains both the MBP-mucin – complex and the MPL-structure of the superficial cells.In the future, studies of the alterations of the salivary mucins and that of the MPL-structure may yield therapeutic opportunities for burning mouth syndrome and perhaps for mucositis causing by irradiation. Focus on cell surface microplication and mucins in oral mucosal biology and oral mucosal diseases is a promising avenue for future research in several ways.The defence architecture of the superficial cells of the oral mucosaP. Asikainen, T.J. Ruotsalainen, J.J.W. Mikkonen, A. Koistinen, C. ten Bruggenkate, A.M. Kullaa10.1016/j.mehy.2012.03.009Medical Hypotheses 78, 6 (2012)2012-04-05Medical Hypotheses2012-04-05786S0306-9877(12)X0005-7Articles790792http://www.medical-hypotheses.com/article/PIIS030698771200117X/abstract?rss=yesAbstract: Cytokines interact with neurotransmitters and modify neuronal and neuroimmune functions. Intense in situ neuronal IL-2 immunoreactivity was detected in vital human brainstem neuronal centers which are principally implicated in cardio-respiratory control mechanisms. These observations were made in critically-ill aging adult as well as in young infant patients dying from various clinico-pathological conditions. We suggested that this in situ cytokine over-expression might tip a delicate balance in molecular interactions in those vital neuro-vegetative centers, causing disturbed homeostatic control of cardio-respiratory functions and impaired arousal responses; we further hypothesized that this IL-2-induced neuro-molecular disequilibrium in the brainstem microenvironment might thus be part of a final common pathway leading to death.Selective expression of a neuromodulatory cytokine (IL-2) in specific brainstem neurovegetative centers: A possible final common neuro-molecular pathway in dying patientsHazim Kadhim, Paul Deltenre, Valérie Segers, Guillaume Sébire10.1016/j.mehy.2012.03.010Medical Hypotheses 78, 6 (2012)2012-04-12Medical Hypotheses2012-04-12786S0306-9877(12)X0005-7Articles793795http://www.medical-hypotheses.com/article/PIIS0306987712001181/abstract?rss=yesAbstract: Epidemiological, experimental and clinical studies support a role for uric acid in acute kidney injury (AKI). We discuss how the conventional role of uric acid in AKI has now evolved from intratubular crystal deposition to pro-inflammatory, anti-angiogenic and immunological function. Data from recent studies are presented to support the hypothesis that uric acid may have a role in AKI via a crystal-independent process in addition to its traditionally accepted role to induce injury via crystal-dependent pathways.Lowering serum uric acid to prevent acute kidney injuryA. Ahsan Ejaz, Bhagwan Dass, Ganesh Kambhampati, Noel I. Ejaz, Natallia Maroz, Gurjit S. Dhatt, Amir A. Arif, Chirag Faldu, Miguel A. Lanaspa, Gaurav Shah, Richard J. Johnson10.1016/j.mehy.2012.03.011Medical Hypotheses 78, 6 (2012)2012-04-16Medical Hypotheses2012-04-16786S0306-9877(12)X0005-7Articles796799http://www.medical-hypotheses.com/article/PIIS030698771200120X/abstract?rss=yesAbstract: In developing kidneys, the total cell population is partly regulated by apoptosis. Despite our understanding of the molecular involvement in the regulatory pathway of apoptosis, we know little about the physiological involvement. Cardiomyocytes express large conductance voltage- and Ca2+-activated K+ (maxi-K+) channels in their inner mitochondrial membranes. Triggering the mitochondrial K+ influx necessary to inhibit apoptosis, the channels play cytoprotective roles during ischemic injury. Since proximal tubular cells in neonatal kidneys are physiologically under hypoxic stress, and since the channel activity is stimulated by hypoxia, those cells would share the same regulatory mechanism of apoptosis with ischemic cardiomyocytes. Therefore, we hypothesize here that the proximal tubular cells in neonatal kidneys would also express the maxi-K+ channels in their inner mitochondrial membranes, and that the channels would play regulatory roles in apoptosis. Our hypothesis is unique because it sheds light for the first time on a physiological mechanism that involves the mitochondrial membranes in developing kidneys. It is also important because the idea could have novel therapeutic implications for kidney diseases that are associated with apoptosis.Inner mitochondrial maxi-K+ channels in neonatal renal tubular cells: Novel therapeutic targets to control apoptosisItsuro Kazama, Yoshio Maruyama10.1016/j.mehy.2012.03.013Medical Hypotheses 78, 6 (2012)2012-04-12Medical Hypotheses2012-04-12786S0306-9877(12)X0005-7Articles800801http://www.medical-hypotheses.com/article/PIIS0306987712001338/abstract?rss=yesAbstract: In this paper, we aimed to present a hypothesis that would explain the mechanism of auditory hallucinations, one of the main symptoms of schizophrenia. We propose that auditory hallucinations arise from abnormalities in the predictive coding which underlies normal perception, specifically, from the absence or attenuation of prediction error. The suggested deficiencies in processing prediction error could arise from (1) abnormal modulation of thalamus by prefrontal cortex, (2) absence or impaired transmission of external input, (3) dysfunction of the auditory and association cortex, (4) neurotransmitter dysfunction and abnormal connectivity, and (5) hyperactivity activity in auditory cortex and broad prior probability. If there is no prediction error, the initially vague prior probability develops into an explicit percept in the absence of external input, as a result of a recursive pathological exchange between auditory and prefrontal cortex. Unlike existing explanations of auditory hallucinations, we propose concrete mechanisms which underlie the imbalance between perceptual expectation and external input. Impaired processing of prediction error is reflected in reduced mismatch negativity and increased tendency to report non-existing meaningful language stimuli in white noise, shown by those suffering from auditory hallucinations. We believe that the expectation–perception model of auditory hallucinations offers a comprehensive explanation of the underpinnings of auditory hallucinations in both patients and those not diagnosed with mental illness. Therefore, our hypothesis has the potential to fill the gaps in the existing knowledge about this distressing phenomenon and contribute to improved effectiveness of treatments, targeting specific mechanisms.Auditory hallucinations: Expectation–perception modelJ.M. Nazimek, M.D. Hunter, P.W.R. Woodruff10.1016/j.mehy.2012.03.014Medical Hypotheses 78, 6 (2012)2012-04-20Medical Hypotheses2012-04-20786S0306-9877(12)X0005-7Articles802810http://www.medical-hypotheses.com/article/PIIS0306987712001363/abstract?rss=yesAbstract: Perineural invasion is a prominent characteristic of pancreatic cancer. Pancreatic cancer has an extremely high incidence of perineural invasion which has been associated with poor survival. Early studies mostly focus on the interaction between cancer cells and nerves. Recently, the effect of pancreatic stellate cells in progression of pancreatic cancer has been paid more attention. Both in vitro studies and in vivo ones revealed that pancreatic stellate cells can enhance the proliferation, migration and invasion of pancreatic cancer cells. Pancreatic stellate cells can also regulate the expression and effect of molecules involved in perineural invasion. In addition, pancreatic stellate cells seems to associated with the generation of neuronal plasticity in pancreatic cancer. Herein the hypothesis that pancreatic stellate cells play a potential role in promote the perineural invasion in pancreatic cancer through three mechanisms. One is that pancreatic stellate cells enhance the proliferation, migration and invasion directly through releasing a variety of stimuli and providing a suitable microenvironment. Pancreatic stellate cells also regulate the expression and effects of molecules involved in perineural invasion such as nerve growth factor. Another is that pancreatic stellate cells induce neuronal plasticity, which makes nerves more vulnerable to be invaded. We can conclude that pancreatic stellate cells play a central role in regulating the perineural invasion process by producing different effects on cancer cells and nerve. To inhibit the activity of pancreatic stellate cells or block the interaction between pancreatic stellate cells and cancer cells or nerve tissue might reduce the perineural invasion in pancreatic cancer.Pancreatic stellate cells promotes the perineural invasion in pancreatic cancerYu Zhou, Quanbo Zhou, Rufu Chen10.1016/j.mehy.2012.03.017Medical Hypotheses 78, 6 (2012)2012-04-18Medical Hypotheses2012-04-18786S0306-9877(12)X0005-7Articles811813http://www.medical-hypotheses.com/article/PIIS0306987712001375/abstract?rss=yesAbstract: Cancer is a leading cause of death worldwide, with a limited cure rate and late diagnosis for certain types of cancer (e.g. pancreatic cancer). As this disease presents an enormous challenge for scientists, new paradigms in oncology are needed to defeat this serious disease. Currently, several peptide drugs are investigated for their preventive, diagnostic and therapeutic properties in oncology, with already 15 peptide drugs marketed for cancer therapy. However, we suggest that quorum-sensing peptide agonists and antagonists can be used in oncology as well, resulting in a larger potential peptide space. This hypothesis is based on (1) the recent evidence of prokaryote–eukaryote signalling by the use of quorum-sensing signalling molecules, (2) the apoptotic phenomenon seen in bacteria, (3) the clear similarities between the bacterial quorum-sensing mechanisms and the metastatic process tumor cells initiate, (4) the multiple receptor targeting and (5) the possibility of pharmacologic manipulation of peptides, resulting in increased receptor targeting.Up till now, however, the use of quorum-sensing signalling peptides in oncology has not yet been investigated, despite the urgent need for new insights in oncology and the promising perspectives.The potential role of quorum-sensing peptides in oncologyE. Wynendaele, E. Pauwels, C. Van de Wiele, C. Burvenich, B. De Spiegeleer10.1016/j.mehy.2012.03.018Medical Hypotheses 78, 6 (2012)2012-04-18Medical Hypotheses2012-04-18786S0306-9877(12)X0005-7Articles814817http://www.medical-hypotheses.com/article/PIIS0306987712001399/abstract?rss=yesAbstract: Irritable Bowel Syndrome (IBS), the most prevalent functional gastrointestinal disorder, is best described by the presence of recurrent symptoms of abdominal pain, diarrhea and/or constipation. It has been thought that IBS is stress-related disorder with no known structural abnormalities, e.g. infectious, biochemical or metabolic causes. But, recent evidence suggests that inflammation within the gastrointestinal tract may be of great importance in the pathogenesis of IBS. Our question is could the conventional and widely available general biological markers of inflammation such as erythrocyte sedimentation rate (ESR) be indicator of microscopic inflammatory process in some IBS patients? We hypothesize that mild inflammation in IBS patients could be detected by meaning of a sensitive but cheap and ubiquitous test – ESR. Furthermore we assume that ESR would be related with the disease severity index and decreased general and disease-specific health-related quality of life (HRQoL). A pilot study has been conducted with 86 outpatients (65% female) with IBS, average age 47.76 (SD=13.68). The preliminary results were partly in favor of our hypothesis. They showed that IBS patients with higher ESR expressed lower disease-specific HRQoL (e.g. they expressed more bowel symptoms, social and emotional disturbances related to disease). No significant correlations were found between ESR and the disease severity as well as general HRQoL.Erythrocyte sedimentation rate – Possible role in determining the existence of the low grade inflammation in Irritable Bowel Syndrome patientsGoran Hauser, Mladenka Tkalcic, Sanda Pletikosic, Nina Grabar, Davor Stimac10.1016/j.mehy.2012.03.020Medical Hypotheses 78, 6 (2012)2012-04-18Medical Hypotheses2012-04-18786S0306-9877(12)X0005-7Articles818820http://www.medical-hypotheses.com/article/PIIS0306987712001065/abstract?rss=yesWe read with great interest the paper by Sui and Zhang published in the January issue of Medical Hypotheses . The authors propose a hypothesis that the cerebellum may play an important role in patients with a vascular dementia, helping with balance, integration and stabilization of brain functions related to cognition. The implication of cerebellum in cognitive and affective functions is widely discussed. Recently, a functional MRI study demonstrated existence of functional topography in the human cerebellum, supporting its role in both motor and cognitive tasks. Cognitive impairments occur, when posterior lobe lesions affect lobules VI and VII, and disrupt cerebro-cerebellar circuits which engage prefrontal and parietal cortices . Taking into consideration the crossed cerebellar diaschisis in patients with unilateral cerebral infarctions, the authors suggest that the improvement of cerebellar dysfunctions may contribute to the treatment of cognitive impairments after stroke. However, it should be mentioned that in cases with unilateral cerebral infarctions, a metabolic and hemodynamic diaschisis occurs in the relevant regions of the contralateral hemisphere. This transhemispheric diaschisis, resulting from lesions of transcallosal connections, may also contribute to the cognitive disorders in stroke patients . Special attention is given to an experimental study showing an improvement of cerebellar dysfunction and cognition after electrical stimulation of the cerebellar fastigial nucleus. The authors assume that this approach may have a beneficial effect in patients with vascular dementia. But it should be mentioned that the electrical stimulation of cerebellar fastigial nucleus, implicated in cerebellar-limbic circuits, may also have a detrimental effect in hypertensive patients because of its powerful effects on systemic blood pressure and cerebral blood follow.Cerebellar dysfunction and cognitive impairments after strokeDimiter I. Hadjiev, Petya P. Mineva10.1016/j.mehy.2012.02.027Medical Hypotheses 78, 6 (2012)2012-03-21Medical Hypotheses2012-03-21786S0306-9877(12)X0005-7Correspondence821821http://www.medical-hypotheses.com/article/PIIS0306987712001077/abstract?rss=yesTinnitus sufferers often have a thorough and expensive workup that does not disclose the cause of their distress. Treatments are frequently ineffective and many suffer indefinitely, living in constant fear that the symptom will only progress. The role of chronic stress in subjective idiopathic tinnitus is poorly understood and may be the missing dimension in the diagnosis and management of this common condition.Tinnitus as a consequence of the fight or flight responseMichael A. Kadoch10.1016/j.mehy.2012.02.028Medical Hypotheses 78, 6 (2012)2012-03-21Medical Hypotheses2012-03-21786S0306-9877(12)X0005-7Correspondence821822http://www.medical-hypotheses.com/article/PIIS0306987712001119/abstract?rss=yesThe development of medical diagnostic devices has been influential in the advance of biomedical engineering research in recent decades. In this paper, we present our hypothesis and prototype development of a novel electronic device for forecasting hypotension episodes caused by acute failures of circulatory function in critically ill patients. Acute hypotension episode (AHE), a clinical condition commonly observed in intensive care units (ICU), characterized by an abnormal low blood pressure values and circulatory collapse is associated with mortality rates as high as 70–90%. Early diagnosis and rapid institution of aggressive therapy offer the best chance for a satisfactory outcome in critically ill patients . Physicians working in ICUs and emergency departments often face difficulties in predicting AHE during the forecast window, i.e. before occurrence of overt hypotension. Invasive direct measures of circulation are generally not a practical option in clinical settings. Recently, computer-based predictive algorithms are presented as potential predictors of AHE, but the predictive accuracy of these models depends on the number of parameters inputted and on pattern recognition and classification algorithms . It is well known that the sympathetic (“fight or flight”) and parasympathetic (“rest and digest”) systems work together in tandem to maintain a state of homeostasis in the body. The galvanic skin response reflects sympathetic tone and is often used as an indirect measure of psychological or physiological arousal . In this brief correspondence, we propose a hypothesis that galvanic skin response-GSR (skin conductance or electrodermal activity) could be used for prediction of AHE in critically ill patients.An innovative device to predict acute hypotension episodes in critically ill patients: hypothesis and prototype developmentK. Subramanya, Altaf Mudhol10.1016/j.mehy.2012.03.004Medical Hypotheses 78, 6 (2012)2012-03-30Medical Hypotheses2012-03-30786S0306-9877(12)X0005-7Correspondence822822http://www.medical-hypotheses.com/article/PIIS0306987712001351/abstract?rss=yesWe read with interest the case report by Madias documenting the novel blood pressure (BP) lowering effects of serial remote ischemic preconditioning (RIPC), including acute reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure, with the potential for longitudinal reductions over time. One area of research that may help inform this observational report involves rhythmic isometric exercise training. A recent meta-analysis, along with numerous small scale mechanistic studies, support the BP lowering effects of rhythmic isometric handgrip (IHG) training, whereby 8–10weeks of thrice weekly training in normotensive and hypertensive populations elicited significant reductions in resting SBP and DBP . Acute IHG exercise also produces small transient reductions in SBP . The typical IHG protocol consists of four 2-min contractions each separated by a short rest period and completed at 30% of maximal voluntary contraction . Isometric exercise, even at low intensities, is sufficient to produce a significant increase in intramuscular pressure and resultant reduction in blood flow, creating ischemic conditions , particularly during the final moments of each 2-min contractions. This creates a feeling of relief when the contraction ends, analogous to the release of the RIPC occlusion cuff, as blood flow to the exercising limb is restored.Serial remote ischemic preconditioning and rhythmic isometric exercise training: A hypothesisPhilip J. Millar, Cheri L. McGowan10.1016/j.mehy.2012.03.016Medical Hypotheses 78, 6 (2012)2012-04-18Medical Hypotheses2012-04-18786S0306-9877(12)X0005-7Correspondence822823