Medical Hypotheses RSS feed: Articles in Press. 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: 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//inpress?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. Medical Hypotheses0306-98772010-09-01 © 2010 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.medical-hypotheses.com/article/PIIS0306987710002902/abstract?rss=yesSummary: Cocaine addiction is a chronic disease marked by relapses, co-morbidities and the importance of psychosocial consequences. The etiology of cocaine addiction is complex and involves three types of factors: environmental factors, factors linked to the specific effects of cocaine and genetic factors. The latter could explain 40–60% of the risk for developing an addiction. Several studies have looked for a link between cocaine addiction and the genes of the dopaminergic system: the genes DRD2, COMT, SLC6A3 (coding for the dopamine transporter DAT) and DBH (coding for the dopamine beta hydroxylase) but unfortunately very few well established results. Pharmacogenetic approach could be an interesting opportunity for the future.The gene DBH has particularly been linked with the psychotic effects caused by cocaine. This so-called cocaine-induced psychosis (CIP) or cocaine-induced paranoia may influence the development of cocaine addiction. Indeed, these psychotic symptoms during cocaine exposure could cause an aversive effect limiting the development of an addiction. Several functional alterations caused by different mutations of the genes involved in dopaminergic transmission (principally-1021C>T of the gene DBH, but also Val158Met of the gene COMT, TaqI A of the gene DRD2 and VNTR 9 repeat of the DAT) could result in a cocaine-induced psychosis prone phenotype.We are hypothesising that the appearance of CIP during the first contact with cocaine is associated with a lower risk of developing cocaine addiction. This protective effect could be associated with the presence of one or more polymorphisms associated with CIP. A pharmacogenetic approach studying combination of polymorphism could isolate a sub-group of patients at risk for CIPs but more favorably protected from developing an addiction. This theory could enable a better understanding of the protective factors against cocaine addiction and offer new therapeutic or preventive targets in vulnerable sub-groups exposed to cocaine.Could the inter-individual variability in cocaine-induced psychotic effects influence the development of cocaine addiction? Towards a new pharmacogenetic approach to addictions - Corrected ProofG. Brousse, F. Vorspan, K. Ksouda, V. Bloch, K. Peoc’h, J.L. Laplanche, S. Mouly, J. Schmidt, P.M. Llorca, J.P. Lepine10.1016/j.mehy.2010.07.043Medical Hypotheses (2010)2010-09-01Medical Hypotheses2010-09-01http://www.medical-hypotheses.com/article/PIIS0306987710002951/abstract?rss=yesSummary: Inhalation of hydrogen gas has been proved to be an effective treatment for ischemia–reperfusion injury. There has been considerable evidence of hydrogen’s protective effect to diseases related to oxidative injury, such as the ischemia–reperfusion injury of the brain, liver and heart. Our previous studies demonstrated that intraperitoneal injection of hydrogen-rich saline protected hypoxic-ischemic brain injury, myocardial and intestine ischemia–reperfusion injury in rats. Bacteria in the large intestinal can produce endogenous hydrogen, and our preliminary experiments revealed that oral administration of mannitol in humans and animals can significantly increase the level of endogenous hydrogen. Therefore, we speculated that oral administration of mannitol may be effective against ischemia–reperfusion injury, which is a convenient, effective and unique treatment for ischemia–reperfusion injury.Oral administration of mannitol may be an effective treatment for ischemia–reperfusion injury - Corrected ProofShulin Liu, Qiang Sun, Hengyi Tao, Xuejun Sun10.1016/j.mehy.2010.07.048Medical Hypotheses (2010)2010-09-01Medical Hypotheses2010-09-01http://www.medical-hypotheses.com/article/PIIS0306987710002987/abstract?rss=yesSummary: Cancer is one of the most serious and merciless health problems of the mankind, about seven million people dying of cancer every year. Two of the most important and promising targets in cancer chemotherapy include DNA alkylating agents and DNA intercalators. The emphasis of this work was to design, synthetize and formulate a mechanism of action for a new class of dual DNA intercalators. The dual DNA intercalators have three main parts: an alkylating unit (represented by two halo-alkyl-ester chains), an intercalator unit (five- or six-membered ring nitrogen heterocycle) and an acetophenone skeleton linker. As mechanism of action, we consider that these compounds act as dual DNA intercalators, the alkylating unit realizing a covalent bonding via DNA protein “cross-linking effect” while nitrogen heterocycles will realize noncovalent bonding via DNA intercalation with purine and pyrimidine bases from DNA and the amino acids from topoisomerases enzymes. Our hypothesis was confirmed by in vitro anticancer tests against HeLa cell lines, where the newly obtained compounds demonstrated a very good activity.Considerations concerning design and mechanism of action of a new class of anticancer dual DNA intercalators - Corrected ProofMihaela Cătălina C. Luca, Vasile V. Tura, Ionel I. Mangalagiu10.1016/j.mehy.2010.07.051Medical Hypotheses (2010)2010-09-01Medical Hypotheses2010-09-01http://www.medical-hypotheses.com/article/PIIS0306987710003087/abstract?rss=yesSummary: Peritoneal dialysis has undergone considerable development from a technological point of view, and osmotic agent has played the essential role in peritoneal dialysis fluid. Because the most commonly used osmotic agent is glucose and icodextrin, there are some disadvantages related to the use of glucose-based solutions and icodextrin. So it is urgent to develop a new peritoneal dialysis osmotic agent. According to these characteristics of glucose and icodextrin, it is promising to explore a better osmotic agent of peritoneal dialysis solution which is able to allow maintenance of the maximum ultrafiltration gradient, and prevent toxicity or accumulation of unwanted substances in the blood, being non-toxic or less-toxic, furthermore the metabolite should not cause significant metabolic disturbance. Maltose may be one of promising osmotic agent and may put an important influence on development of peritoneal dialysis.Maltose, a promising osmotic agent in peritoneal dialysis solution - Corrected ProofZhan-Jun Shu, You-Ming Peng, Lin Sun, Li Xiao, Ying-hong Liu, Jun Li, Guang-hui Ling, Wen-bin Tang, Upur Halmurat, Fu-you Liu10.1016/j.mehy.2010.08.007Medical Hypotheses (2010)2010-09-01Medical Hypotheses2010-09-01http://www.medical-hypotheses.com/article/PIIS030698771000318X/abstract?rss=yesSummary: Sex hormones play an important role in coronary artery disease. Although both male and female hormones have been well-documented to be able to influence vascular biology, the preventive use of sex hormones in CAD is not established. Recent progress suggests a necessity of rethinking of the use of sex hormones for CAD in both sexes. We hypothesize that a long-term and appropriate low-dose combination of male hormone and female hormone could be an effective preventive strategy for men with a high risk of but not developed CAD. This hypothesis is supported by the fact that estrogen has favorable profiles on several key CAD-associated risk factors regardless of sexes. Testosterone supplementation has been linked to a reduced risk of CAD specifically in men. In animal models the reduced risk of CAD in males administrated with testosterone is due to the conversion of testosterone into estrogen; and sex hormone ratio changes rather than each individual sex hormone were found to be the predictor of CAD in a human study, suggesting the importance of a proper ratio of estrogen:testosterone in the development of CAD. In addition, the controversy surrounding the use of hormone replacement therapy in women in turn indicates a potential beneficial effect of sex hormones in men in the prevention of CAD because of the fundamental difference between sexes. Therefore, the combined use of estrogen and testosterone for CAD in men deserves a full investigation and could provide useful information in understanding of the preventive and/or therapeutic application of sex hormones in both sexes.Prevention of coronary artery disease in men: Male hormone, female hormone, or both? - Corrected ProofChangsheng Yang, Xiaoping Wang, Changming Geng, Hongliu Ding10.1016/j.mehy.2010.07.053Medical Hypotheses (2010)2010-09-01Medical Hypotheses2010-09-01http://www.medical-hypotheses.com/article/PIIS0306987710002938/abstract?rss=yesSummary: The role of cone beam computed tomography (CBCT) in imaging of the oral and maxillofacial region is well known and its indications and possibilities are still increasing. More sophisticated technologies are being developed each year, mainly providing higher resolution, bigger field of view, faster scanning and better scatter reduction. One of the major problems remaining to be solved is the unwanted movement of the patient during the scanning procedure. All hardware solutions that have been developed to fix the patient’s head in a steady position have their limits. For example, they cannot eliminate small movements caused by breathing, heartbeat, and swallowing. We have developed a simple method to improve these CBCT images. The movement of the scanned object is monitored with marks attached to it. These marks are identified on every 2D image captured during the scanning procedure and used to unify the position of these 2D images. The final 3D reconstruction produces a sharper 3D data set with higher resolution and reduced blur. In conclusion, this simple method has the potential to improve the quality of CBCT scans.Reduction of the negative influence of patient motion on quality of CBCT scan - Corrected ProofTomáš Hanzelka, René Foltán, Edita Horká, Jiří Šedý10.1016/j.mehy.2010.07.046Medical Hypotheses (2010)2010-08-30Medical Hypotheses2010-08-30http://www.medical-hypotheses.com/article/PIIS0306987710002744/abstract?rss=yesSummary: The modern living standard has imposed upon society a situation of chronic sleep deprivation. This chronic loss of sleep affects women more than it does men. As a result, the postponement of pregnancy has become a common choice due to the priority given to social and domestic activities. For women, pregnancy represents a condition of intense physical and physiological changes that subject the pregnant woman to a number of potentially stressful situations, ultimately interfering with their quality of sleep. Chronic sleep deprivation, along with the changes imposed on women through pregnancy, can lead to several harmful consequences for the pregnant woman and the child, and can potentially undermine the mother–infant relationship. This article discusses circumstances under which sleep deprivation and poor sleep quality during pregnancy could result in damage to the mother–infant relationship, specifically through maternal fatigue, postpartum depression and changes in pregnancy-related hormonal secretions and activity.Sleep impairment during pregnancy: Possible implications on mother–infant relationship - Corrected ProofGabriel Natan Pires, Monica Levy Andersen, Márcia Giovenardi, Sergio Tufik10.1016/j.mehy.2010.07.036Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS030698771000294X/abstract?rss=yesSummary: Evidence of immune stimulation has been noted in opiate dependent patients for many decades. Documented changes have included lymphadenopathy, round cell infiltration of the hepatic portal triads, diffuse peri-bronchitis, hyperglobulinaemia, lymphocytosis, monocytosis, systemic cytokine stimulation, and cytokine and chemokine activation within the neuraxis. A parallel literature describes an elevated list of chronic degenerative disease as common in such patients including neurodegenerative conditions, atherosclerosis, nephrosclerosis, hepatic fibrosis and cirrhosis, chronic obstructive and fibrotic lung disease, osteoporosis, chronic periodontitis, various cancers, hair greying, and stem cell suppression. All of these disorders are now known to have an important immunological role in their pathogenic pathways. The multisystem nature of these myriad changes strongly suggest that the ageing process itself is stimulated in these patients. The link between the immunostimulation on the one hand and the elevated and temporally advanced nature of the chronic degenerative diseases on the other appears not to have been made in the literature. Moreover as immunostimulation is also believed to be an important, potent and principal contributor to the ageing process it appears that experimental and studies of this putative link are warranted. Verification of such an hypothesis would also carry management implications for dose and duration of chronic pain and addiction treatment, pharmacotherapeutic selection, and novel treatments such as long term naltrexone implant therapy and heroin trials.Chronic immune stimulation as a contributing cause of chronic disease in opiate addiction including multi-system ageing - Corrected ProofAlbert Stuart Reece10.1016/j.mehy.2010.07.047Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003038/abstract?rss=yesSummary: Yawning continues to pose as a scientist’s conundrum. Evidence is presented of yawning and contagious yawning in a number of different neurological disorders. Explanations are discussed in the context of disparate neurological disorders together with proposals for how theses findings may be linked. Thus, greater understanding of yawning and of neurological disorders may be achieved by exploring common neuro-chemical pathways and the involvement of neurotransmitters that are implicated in these different disorders. Finally, contagious yawning is discussed in the context of the susceptibility of persons and the similarity this presents with our understanding of the mechanisms involved in hypnosis.The dawn of the yawn: Is yawning a warning? Linking neurological disorders - Corrected ProofSimon B.N. Thompson10.1016/j.mehy.2010.08.002Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003063/abstract?rss=yesSummary: Cardiac risk stratification is the attempt to delineate who is at risk of cardiac event and who is not. Increasingly, the medical literature is filled with novel methods and markers of baseline risk assessment. This body of literature has been criticized broadly for making claims beyond what is statistically justified. In this hypothesis, we will explore an alterative explanation for the limitations of baseline risk assessment. I will contend that current risk models commit a logical error called the Concorde fallacy. The role of risk topography will be suggested as a novel method to rescue cardiac risk models.Baseline event rate, the Concorde fallacy, and the topography of cardiac risk - Corrected ProofVinay Prasad10.1016/j.mehy.2010.08.005Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003075/abstract?rss=yesSummary: Chondrogenic dwarfism in Morquio disease (mucopolysaccharidosis IV) has been suggested to be strongly linked to the abnormal lysosomal storage of cartilaginous extracellular matrix waste products within chondrocytes and fibroblasts. The specific genetic defects of enzymes of the keratan sulfate and chondroitin-6-sulfate metabolism have been detected at the molecular level and importantly contributed to the current knowledge on the phenotype of this rare metabolic disorder. However, the pathogenesis of this epiphyseal centered progressive skeletal disease does not seem to be fully explained by the dysfunction of the chondrocyte cytoplasm that presents with vacuolar changes in adult patients. I propose that the accumulation of extracellular matrix degradation product-laden macrophages within epiphyseal cartilage canals during the early postnatal period causes dysregulation in the synchronized process of the neoformation and resorption of the maturing radial growing epiphyses. Similarly, the resorption of pannus tissue following the microtraumatisation of weight-bearing joints and epiphysis-type bones becomes impacted. If the hypothesis is valid, the early pathogenesis in Morquio disease could be because of the inadequate regression of cartilage canals and impaired resorption and restitution of pannus tissue.Morquio disease: The role of cartilage canals in the pathogenesis of chondrogenic dwarfism - Corrected ProofJozef Zustin10.1016/j.mehy.2010.08.006Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003099/abstract?rss=yesSummary: Butyrylcholinesterase may have a role in a number of metabolic functions and could affect the expression of insulin resistance syndrome. We present our integrated work using clinical, biochemical and bioinformatic approaches to delineate the possible function of this enzyme. Initially, we constructed a phylogenic tree with nucleotides and amino acid sequences and showed the existence of similar sequences in bacteria, plants and in other animals. We also demonstrated a possible pathogenic role for BChE in the common existence of insulin resistance, type 2 diabetes and Alzheimer’s disease by in silico method and followed it up with a diabetic mouse study where cognition was slowed along with changes in BChE levels. In the next group of in silico studies, we employed THEMATICS method to identify the amino acids at the active site and later performed docking studies with drugs. THEMATICS predicted two clusters of ionisable amino acid residues that are in proximity: one with two residues and another with 11 showed perturbation in the THEMATICS curves. Using ISIS/Draw 2.5SP4, ARGUSLAB 4.0.1 and HEX 5.1. software. 3-D ligands were docked with BChE motif (from PDB). We did not find any of the ligands studied with significant docking distance, indicating they did not have direct interaction with the active site. Subsequently we performed in silico studies to compare the secondary structure and domain of BChE. Protein–protein interaction showed the following intersections with BChE UBE21, CHAT, APOE, AATF, DF ALDH9A1, PDHX, PONI PSME3 and ATP6VOA2. The integrative physiological roles of proteins with poorly known functions can be approached by generating leads in silico, which can be studied in vivo, setting into movement an iterative process.Butyrylcholinesterase in metabolic syndrome - Corrected ProofGumpeny R. Sridhar, Allam Appa Rao, Kudipudi Srinivas, Gumpeny Nirmala, Gumpeny Lakshmi, Dasika Suryanarayna, Padmanabhuni V. Nageswara Rao, Dowluru G.S.V.G.L. Kaladhar, Sali Veeresh Kumar, Tatavarthi Uma Devi, Turaga Nitesh, Thota Hanuman10.1016/j.mehy.2010.08.008Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003105/abstract?rss=yesAzoospermia is found in 15–20% of male infertility . Azoospermia can be classified into obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) according to whether there are obstructions in the seminal duct. Approximately 40% azoospermic patients have OA; the other 60% who suffer from spermatogenic failure caused by testicular dysfunction or sex hormone disorders are classified into NOA . The correct classification is very important since the further clinical treatments and prognosis differ totally for the two types of azoospermia . Testicular fine needle aspirations (TEFNA) and vasoseminal vesiculography are relatively accurate to differentially diagnose azoospermia . However, they are invasive inspections and are unacceptable to some patients. Determination of fructose concentration in seminal plasma has recently been generally accepted as a non-invasive method for finding obstructions in the seminal duct . As a kind of seminal plasma protein secreted specifically by seminal vesicle, reduced fructose concentration often means that there are obstructions in the seminal vesicle or distal duct. However, fructose content in seminal plasma could be normal in OA cases with obstructions in the epididymis or vas deferens, which affects its diagnostic accuracy and value.Eppin, a novel marker to differentially diagnose azoospermia? - Corrected ProofBianjiang Liu, Zengjun Wang, Wei Zhang10.1016/j.mehy.2010.08.009Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS0306987710003130/abstract?rss=yesSummary: Bioreactor, which is used for in vitro construction of tissue-engineered cartilage, has been extensively studied by researchers. The growth and development of articular cartilage tissue are affected by biomechanical and biochemical factors, especially mechanical condition. Kinds of mechanical conditions including compressive and shear force, fluid flow, hydrostatic pressure, and tissue deformation, were developed in the past years. However, most mechanical conditions of improved bioreactor involve only one or two external force, which is merely partial for engineering cartilage tissue. No bioreactor which can simulate a normal articular cartilage in terms of structure and function has been reported. Consequently, simulation of bionic mechanical environment of a normal articular cartilage is considered to be the optimal environment for culturing the functional articular cartilage in vitro. Based upon this purpose, we designed a rolling-compression loading bioreactor. It could provide cultures with multi-mechanical stimulations and sufficiently mimic the complex mechanical environment of a normal articular cartilage. We propose that this comprehensive rolling-compression loading bioreactor can enhance the cultivation of functional cartilage constructs in vitro.Culturing functional cartilage tissue under a novel bionic mechanical condition - Corrected ProofMinglin Sun, Dan Lv, Chunqiu Zhang, Lei Zhu10.1016/j.mehy.2010.08.011Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003142/abstract?rss=yesSummary: A given cancer is produced by a unique combination of genetic alterations that target specific genes, most often leading to activation of oncogenes and inactivation of tumor suppressor genes. Traditional oncogenes, such as RasV12, are involved in maintaining pro-survival and proliferation signals activated in the cell. Several evidences suggest that cancer cells are addicted to oncogenes and that their inhibition has dramatic effects on cancer cells. Here, the hypothesis that oncogenes may be activated only transiently and that this short activation may be important for cancer formation by affecting the differentiation state of the cancer cells is presented. These “transient oncogenes” are overlooked in genomic or proteomic analysis due to their transient nature. Here we argue that transcription factors, such as the so called Yamanaka factors, capable of reprogramming cells to a less differentiated state, which normally happens to cancer cells, can function as transient oncogenes. Several published evidences are used to support the proposed hypothesis. Analysis and even targeting of this new class of oncogenes could have a great impact on cancer biology, treatment and, most importantly, prevention.Transient oncogenes - Corrected ProofG. Lenz10.1016/j.mehy.2010.08.012Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003178/abstract?rss=yesAbstract: Tissue-engineering strategies to restore the periodontal defects are being developed. It will result in the periodontal formation and growing new function tissue rather than new replacement of periodontium. Although a number of procedures have been investigated in an attempt to regenerate lost periodontal tissue, none has yet led to new cementum formation, remodeling of the periodontal ligament, and new bone formation in clinic. Dental follicle cells (DFCs), as a progenitor cell of periodontal ligament cell and stem cell, have more potential abilities than PDL-cell in formation of periodontal tissue. More researches focus on the inductive environments, such as bone morphogenetic protein-2 (BMP-2), dexamethasone, and transfer growth factor, and scaffold. We hypotheses that DFCs from Beagle’s dog are isolated, induced by BMP-2, basic-fibroblast growth factor and dexamethasone, and seeded by beta-tricalcium phosphate ceramic (beta-TCP), then the complex was auto-implanted into the periodontal defects in the same Beagle’s dog to observe the regeneration of periodontal tissue in vivo. The study will explore the feasibility and application of restore of periodontal defects by DFCs–beta-TCP complex. We believe it is especially helpful to future clinical study and application.Dental follicle cells combined with beta-tricalcium phosphate ceramic: A novel available therapeutic strategy to restore periodontal defects - Corrected ProofJin Zuolin, Qian Hong, Tan Jiali10.1016/j.mehy.2010.08.015Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27http://www.medical-hypotheses.com/article/PIIS0306987710003191/abstract?rss=yesUric acid as the derivatives of adenine- and guanine-based purine compounds is responsible for 30–65% of the peroxyl radical-scavenging capacity of blood plasma . The antioxidant role of uric acid lies in its strong activity of scavenging peroxynitrite, hydroxyl radical and singlet oxygen, and chelate transitionmetals .Moderate levels of plasma uric acid could promote fracture healing - Corrected ProofM.M. Li Donghui10.1016/j.mehy.2010.07.054Medical Hypotheses (2010)2010-08-27Medical Hypotheses2010-08-27CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS030698771000304X/abstract?rss=yesSummary: Biologic agents, especially TNFα inhibitors, appear to be very effective in treatment of rheumatoid arthritis (RA). Although the use of biologic agents has greatly improved the therapeutic efficacy in management of RA, biologic therapies for RA treatment have several limitations. These agents fail to achieve complete remission in substantial portion of RA patients. Also certain adverse events have been observed, including serious bacterial infections and reactivation of latent tuberculosis. Previous reports demonstrated that TNFα inhibitors are more efficacious in combination with other drugs such as methotrexate. In this report, we suggest that paricalcitol, a synthetic vitamin D analog is another candidate molecule for combination therapy with TNFα inhibitors in RA.Paricalcitol, a synthetic vitamin D analog: A candidate for combination therapy with biological agents in rheumatoid arthritis - Corrected ProofTae-Hwan Kim, Jong Dae Ji10.1016/j.mehy.2010.08.003Medical Hypotheses (2010)2010-08-26Medical Hypotheses2010-08-26http://www.medical-hypotheses.com/article/PIIS0306987710002422/abstract?rss=yesSummary: The hypothesis states that infantile colic is a pain syndrome and the excessive crying leads to aerophagia and abdominal discomfort. The pain comes from sucking the bottle or the nipple. Feeding for the infant is a heavy workload for the masticatory muscles.The tiny digastricus muscle moves the hyoid bone, takes part in opening the mouth and retrusion of the mandible and assists in mowing the tongue upward, forward and backwards. In the adult population pain from this muscle is well documented. The hypothesis explains the crying as being due to muscular pain at first, later on pain from the origins and insertions of the muscle. Then with increased muscular strength and development the pain fades away.Infantile colic: Is a pain syndrome - Corrected ProofGardar Gudmundsson10.1016/j.mehy.2010.07.014Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23http://www.medical-hypotheses.com/article/PIIS030698771000263X/abstract?rss=yesSummary: Awareness under anaesthesia is an uncommon but serious phenomenon, which continues to occur despite the use of commercially available depth-of-anaesthesia (DOA) monitors. Many of these monitors use processed electroencephalographic (EEG) data to give an indication of anaesthetic depth. They all suffer from error due to electrical interference, individual variation and the inevitable inaccuracy inherent in the rendering of complex waveforms into a simplified digital score. It is recognised that, in the processing of complex analogue audio waveforms (i.e. sound), the human ear consistently outperforms the computer. I hypothesise that an audio signal derived from the raw EEG waveform could form the basis of a DOA monitor, enabling humans to directly determine whether a patient is awake or anaesthetised from sound alone. I propose to call the sounds derived from amplification of the EEG trace the ‘audio EEG’.Use of audio signals derived from electroencephalographic recordings as a novel ‘depth of anaesthesia’ monitor - Corrected ProofJohn Glen10.1016/j.mehy.2010.07.025Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23http://www.medical-hypotheses.com/article/PIIS0306987710002847/abstract?rss=yesThe second paragraph of column 1, page 830 should read: In boys and girls, the ratio of T/EpiT in plasma is⩾1 in childhood, but increases dramatically in males during prepuberty and puberty, remaining constant in adulthood [2]. Unlike T or 5ά-dihydrotestosterone (5ά-DHT), there is no discernible decrease in EpiT levels in males after age 50 [1]. It has been said that this points to some significance of EpiT in males before puberty when it may attenuate the effects of T [2]. Although the pathway of EpiT production in females is unknown, as in males, a sharp increase in the T/EpiT ratio occurs before puberty [2]. From puberty until senescence, EpiT levels remain about the same. Considering the antiandrogenic effects of EpiT, an increased T/EpiT ratio may expose sexually dimorphic brain regions to the deleterious effects of T or its intermediates, suggesting that EpiT modulates the action of T during critical periods in brain development.Erratum to: Sex, drugs, and sport: prostaglandins, epitestosterone, and sexual development. Med Hypotheses 2007;69:829–835 - Corrected ProofBryan K. Sanders10.1016/j.mehy.2010.07.037Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23ERRATUMhttp://www.medical-hypotheses.com/article/PIIS0306987710002859/abstract?rss=yesSummary: Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeutic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Meanwhile, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immediately administered on suspicion of acute stroke, including AIS and AHS.Edaravone: A new therapeutic approach for the treatment of acute stroke - Corrected ProofKiyoshi Kikuchi, Ko-ichi Kawahara, Naohisa Miyagi, Hisaaki Uchikado, Terukazu Kuramoto, Yoko Morimoto, Salunya Tancharoen, Naoki Miura, Kazunori Takenouchi, Yoko Oyama, Binita Shrestha, Fumiyo Matsuda, Yoshihiro Yoshida, Shinichiro Arimura, Kentaro Mera, Ko-ichi Tada, Narimasa Yoshinaga, Ryuichi Maenosono, Yoshiko Ohno, Teruto Hashiguchi, Ikuro Maruyama, Minoru Shigemori10.1016/j.mehy.2010.07.038Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23http://www.medical-hypotheses.com/article/PIIS0306987710002914/abstract?rss=yesSummary: Mucopolysaccharidoses (MPS) are inherited metabolic disorders from the group of lysosomal storage diseases (LSD). They arise from mutations causing dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs) in lysosomes. Impaired degradation of these compounds results in their accumulation in cells and dysfunction of most tissues and organs of patients. If heparan sulfate (HS) is the sole or one of stored GAGs, brain functions are also affected. However, despite the fact that products of incomplete degradation of the same chemical, HS, are accumulated in brains of patients suffering from Hurler disease (MPS type I), Hunter disease (MPS type II), Sanfilippo disease (MPS type III) and Sly disease (MPS type VII), and obvious deterioration of brain functions occur in these patients, their behavior is considerably different between various types of MPS. Here we asked the question about biochemical reasons of these differences. We performed theoretical analysis of products of incomplete HS degradation that accumulate in tissues of patients diagnosed for these diseases. A correlation between chemical structures of incompletely degraded HS and behaviors of patients suffering from particular MPS types was found. We propose a hypothesis that particular chemical moieties occurring at the ends of incompletely degraded HS molecules may determine characteristic behavioral disturbances, perhaps due to chemical reactions interfering with functions of neurons in the brain. A possible experimental testing of this hypothesis is also proposed. If the hypothesis is true, it might shed some new light on biochemical mechanisms of behavioral problems occurring not only in MPS but also in some other diseases.Why are behaviors of children suffering from various neuronopathic types of mucopolysaccharidoses different? - Corrected ProofGrzegorz Węgrzyn, Joanna Jakóbkiewicz-Banecka, Magdalena Narajczyk, Andrzej Wiśniewski, Ewa Piotrowska, Magdalena Gabig-Cimińska, Anna Kloska, Monika Słomińska-Wojewódzka, Anna Korzon-Burakowska, Alicja Węgrzyn10.1016/j.mehy.2010.07.044Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23http://www.medical-hypotheses.com/article/PIIS0306987710002926/abstract?rss=yesThe concern about the recent increase of behaviors related to a lack of self-control in post-industrialized societies is linked to the old idea of achieving self-restraint that preoccupied all ethical and moral doctrines throughout the history. But it is only since the nineteenth century the concepts of impulsivity and impulsive acts (especially in the Occidental realm, i.e., in the Western culture, and in the biomedical setting) have described the lack of self-control . The French word “impulsion” (impulsivity as a state or an act), frequently used by the nineteenth century French alienists, had been imported from mechanics. In fact, in the modern era, mechanical models became attractive when trying to depict the nature of reality (e.g., Descartes models). Nowadays, impulsivity is mainly studied both as a personality dimension included in several diagnostic conditions, and as a diagnostic category itself (“Impulse Control Disorders”) .Post-industrialized societies and impulsivity - Corrected ProofMaría Dolores Braquehais, Leo Sher10.1016/j.mehy.2010.07.045Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS0306987710002975/abstract?rss=yesSummary: Evolutionary Medicine can be useful when analysing the origin of disease and symptoms. Acute urticaria or anaphylaxis is bothersome and potentially life-threatening. We analyse this symptom-complex in the context of Gastro-allergic Anisakiasis (GAA), where the human is an incidental host for the cosmopolitan fish-nematode Anisakis simplex (A. simplex). The immunological response against this nematode resembles that against other helminths, but overt expression of allergic symptoms is by far more frequent in GAA. This could be due to the missing co-evolutionary relationship between host and parasite. Features of acute gastric parasitism with and without overt allergic type 1 hypersensitivity symptoms are compared with the abdominal complications in intestinal Anisakiasis, where clinically visible IgE mediated symptoms are missing. In GAA, parasite induced chronic abdominal complications are missing. We postulate that urticaria in GAA can be considered the price for rapidly expelling the live larva of A. simplex in those subjects whose evolutionary history made them more resistant to other helminth parasites. Further, urticaria is explained as a possibly exaggerated immunopathological feature in this special type of acute parasitism, where sensitized mast-cells are not only present in the skin, but also in the gastro-intestinal mucosa. This evolutionary analysis of clinical observations is the first known report that addresses the possible beneficial feature of hypersensitivity type 1 response with overt allergic urticaria-anaphylaxis in GAA and confers an evolutionary based sense to the acute IgE-mediated reaction.The hidden sense of symptoms: Urticaria can be beneficial - Corrected ProofAlvaro Daschner, Carmen Cuéllar10.1016/j.mehy.2010.07.050Medical Hypotheses (2010)2010-08-23Medical Hypotheses2010-08-23http://www.medical-hypotheses.com/article/PIIS0306987710002860/abstract?rss=yesSummary: In-depth researches on the psychopathology of obsessive–compulsive disorder (OCD) have been made in the cognitive-behavioral domain. However, some questions about the symptoms have not been properly answered yet. Studies from other domains also shed light on the psychopathology of OCD. The most inspiring ones are studies on psychological trauma which have probed into the mechanism of intrusions, and studies on emotion regulation which have investigated how behavioral emotion expressions are shaped. In this paper, we analyze the roles of psychological trauma and emotion regulation in OCD and propose a double conflicts model. In the model, it is hypothesized that information conflict and motivational conflict, which are called “core conflicts”, are key factors in the psychopathology of OCD, and that obsessions and compulsions arise within two associated loops. Anxiety ratification therapy hypothesis is further put forward, which emphasizes the acceptance of all aspects of anxiety, including the behavioral responses and the accompanying new information, and sets the modification of the basic assumptions as the goal of treatment. Although the model provides comprehensive explanation for many symptoms, the assumptions on which the model is based are in need of confirmation. The therapy is tailored for OCD, but its operability and effect should be monitored closely.Double conflicts model and anxiety ratification therapy hypotheses of obsessive–compulsive disorder - Corrected ProofZhong-Ming Zhang, Zhong-Liang Zhang, Hong Li10.1016/j.mehy.2010.07.039Medical Hypotheses (2010)2010-08-18Medical Hypotheses2010-08-18http://www.medical-hypotheses.com/article/PIIS0306987710002884/abstract?rss=yesSummary: Although the etiology of systemic lupus erythematosus (SLE) remains to be fully elucidated, it is now apparent that multiple genetic and environmental factors are at play. Because lupus has a strong female preponderance, several studies have examined the role of female hormones in disease etiology. Yet this knowledge has not helped to explain lupus etiology or to prevent it. Estrogens exist not only as natural or drug compounds, but also as environmental chemical contaminant and women are highly exposed to all of them. Estrogenic activity has been found in a number of pesticides including pyrethroids that are largely used in the household. Although there is only a small amount of published data examining a possible causal relationship between lupus and pesticides it can be hypothesized that pesticides, in particular insecticides, through their estrogenic activity and capacity to induce oxidative stress provoke autoimmune reaction influencing lupus development.Lupus erythematosus. Are residential insecticides exposure the missing link? - Corrected ProofCristina Fortes10.1016/j.mehy.2010.07.041Medical Hypotheses (2010)2010-08-18Medical Hypotheses2010-08-18http://www.medical-hypotheses.com/article/PIIS0306987710002872/abstract?rss=yesCerebral salt wasting (CSW) is an important, underestimated cause of hyponatremia characterized by hypersecretion of atrial natriuretic peptide (ANP), and is seen primarily in association with central nervous system disorders . Distinguishing CSW from hyponatremia secondary to circulating volume depletion or from syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is crucial, since quite different treatments are required. Reports of the existence of CSW in the pediatric population are rare and uncommon in newborn infants . Hypernatremia and hyperbilirubinemia have not been reported as etiologic factors of CSW in newborns. Use of fludrocortisone in patients with CSW has hitherto been reported only in a few isolated pediatric populations . Herein, we describe a newborn who was treated successfully by fludrocortisone with CSW as a result of hypernatremia and severe hyperbilirubinemia.Fludrocortisone therapy in a newborn with cerebral salt wasting due to hypernatremia and severe hyperbilirubinemia - Corrected ProofAhmet Karadag, Yilmaz Tabel, Derya Gumus Dogan, Mumtaz Aktas, Mehmet Aslan, Metin Dogan10.1016/j.mehy.2010.07.040Medical Hypotheses (2010)2010-08-17Medical Hypotheses2010-08-17CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS0306987710002665/abstract?rss=yesSummary: Hepatic inflow occlusion during the liver surgery may result in a transient ischemia period followed by reperfusion, and may initiate liver injury and lead to postoperative liver dysfunction. Especially in cirrhotic patients, the tolerance time of ischemia is much shorter and the outcome would be worse. Recently, clinical trials had proved that volatile anesthetics rather than propofol can protect myocardial cells from ischemia reperfusion (IR) injury in cardiac surgery. Meanwhile, animal studies had revealed that volatile anesthetics could induce some endogenous protective molecules in the liver such as hypoxia induced factor-1 (HIF-1), heme oxygenase (HO) enzyme system and inducible nitric oxide synthase (iNOS), which make the volatile anesthetics posing the extraordinary anti-oxidative, anti-inflammatory, anti-apoptotic, and vasodilatory characteristics. However, there is still lack of trials to compare the postoperative outcomes such as liver function in cirrhotic patients undergoing liver surgery with inflow occlusion between volatile anesthetics and propofol anesthesia. Hence we hypothesize that with its anti-IR injury characteristics, volatile anesthetics might be the more appropriate choice in cirrhotic patients undergoing liver surgery with occlusion.Volatile anesthetics might be more beneficial than propofol for postoperative liver function in cirrhotic patients receiving hepatectomy - Corrected ProofK.M. Tao, L.Q. Yang, Y.T. Liu, Y. Tao, J.C. Song, F.X. Wu, W.F. Yu10.1016/j.mehy.2010.07.028Medical Hypotheses (2010)2010-08-16Medical Hypotheses2010-08-16http://www.medical-hypotheses.com/article/PIIS0306987710002690/abstract?rss=yesSummary: Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium.There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients.Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open.The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase.The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients.Acute coagulopathy of trauma: Balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation - Corrected ProofP.I. Johansson, S.R. Ostrowski10.1016/j.mehy.2010.07.031Medical Hypotheses (2010)2010-08-16Medical Hypotheses2010-08-16http://www.medical-hypotheses.com/article/PIIS0306987710002719/abstract?rss=yesSummary: Persecutory ideation is one of the most commonly reported psychiatric symptoms in individuals with schizophrenia and is associated with significant patient distress and impairment. Therefore, much attention has recently been devoted to theoretical explanations of persecutory ideation that can help inform and guide patient care. A cognitive model of persecutory ideation suggests that individuals with psychosis who experience anxiety along with other stressors are at increased risk for developing intense “threat” or persecutory beliefs. Correlational studies have found evidence for this proposed link between anxiety levels and the persistence, distress levels, and degree of conviction associated with persecutory ideation. Importantly, recent research has found support for a possible prospective/causal role for anxiety in the generation and maintenance of paranoid beliefs. Existing interventions for persecutory ideation consist of pharmacological treatments that have variable efficacy and often entail serious side-effects, and cognitive behavioral treatments (CBT) that target persecutory thoughts, but are often unavailable, require high level of clinician expertise, and may be difficult to conduct with patients who are cognitively impaired or apprehensive about openly exploring their paranoid beliefs. Given the empirical support for a prospective relationship between anxiety and persecutory ideation, it is reasonable to predict that clinicians could impact persecutory ideations indirectly by making good use of existing evidence-based interventions for anxiety. Progressive Muscle Relaxation (PMR) is an effective method for reducing physiological arousal and treating various anxiety disorders, and has been shown to be feasible with patients with psychosis. We offer that exportability and ease of use makes PMR a promising intervention for mental health practitioners to target anxiety precipitating persecutory ideation. We hypothesize that PMR could be used to help ameliorate anxiety in patients who are at risk or already experiencing persecutory ideation, subsequently reducing the frequency, level of conviction, and distress associated with persecutory thoughts. Our hypothesis could be tested through feasibility and randomized control trials of PMR for treatment of persecutory ideation in individuals with schizophrenia. We expect the relationship between PMR and persecutory ideation will be mediated by reduction in anxiety. Potential advantages of examining our hypothesis include identifying a viable, efficacious, cost-effective novel intervention for paranoia in patients with psychosis. In addition, PMR could be easily facilitated by practitioners with varying levels of training and integrated with other existing interventions for persecutory ideation.A possible role for Progressive Muscle Relaxation in the treatment of persecutory ideation - Corrected ProofDror Ben-Zeev, Jonathan Larson, Meagan Sarratt10.1016/j.mehy.2010.07.033Medical Hypotheses (2010)2010-08-16Medical Hypotheses2010-08-16http://www.medical-hypotheses.com/article/PIIS0306987710002896/abstract?rss=yesSummary: Over a century after Freud’s attempt to establish psychoanalysis as a natural science, there is renewed interest in the integration of psychoanalytic and neuroscientific findings within a single theoretical and experimental framework. However, it is important that any intellectual exchange is not motivated only by declining confidence in psychoanalytic theory and practice or awareness of the rising fortunes of the brain sciences. The present paper considers three possible ways in which psychoanalysis and neuroscience might be integrated. These include the investigation of the neurological organisation of psychoanalytically defined phenomena; the evaluation of psychoanalytic theories based on their neurobiological evidence; and the use of neuroimaging techniques to assess the progress and outcome of psychoanalytic treatment. The author argues that these exercises are unlikely to provide psychoanalysis with the “unlimited opportunities for overcoming its uncertainties and doubts” that some have anticipated. For instance, the argument that mapping psychoanalytically defined phenomena in the brain may provide biological validity to these phenomena should be considered an expression of logical confusion; the evaluation of psychoanalytic theories based on their biological evidence is critically dependent on speculative interpretation of what the theories predict at neuronal level; and the supposedly objective evaluation of the progress and outcome of psychoanalytic treatment on the basis of neurobiological data relies on the subjective reports of the patient and analyst. In light of this conclusion, there are a number of outstanding questions which remain to be addressed, including whether psychoanalysis should adhere to scientific canons and whether this would necessarily require an experimental methodology.Psychoanalysis on the couch: Can neuroscience provide the answers? - Corrected ProofAndrea Mechelli10.1016/j.mehy.2010.07.042Medical Hypotheses (2010)2010-08-16Medical Hypotheses2010-08-16http://www.medical-hypotheses.com/article/PIIS030698770900382X/abstract?rss=yesSummary: No satisfactory explanation has been offered, to date, to account for the prevalence of the haemochromatosis genes in the European population and yet relative paucity of the gene in the tropics. Traditional wisdom suggests that, in antiquity, the haemochromatosis gene, which promotes iron absorption, would have protected ancient man from iron loss resulting from injury either during hunting or through war. However, such an advantage would be equally desirable for other populations where the incidence of the alleles is negligible. Others have tackled the polemic from the another view, postulating that the paucity of the haemochromatosis alleles in populations outside of Europe may be explained by the fact that iron load predisposes to infection and that iron deficiency anaemia is protective against this by limiting parasitic access to host stores of iron. This explanation alone is equally unsatisfactory as European populations are exposed to pathogens and would benefit from any protection afforded by mild anaemia. Others have mooted genetic drift as another alternative explanation. Yet this would be unexpected for a gene which is deleterious.We propose here that the driving force for the propagation of the haemochromatosis alleles was not infection per se but the nature of the parasitic fauna which sojourned with mankind. The tropics are inhabited with multicellular parasitic and highly pathogenic organisms, which consequently have a high demand for iron. The organisms have developed aggressive means of iron extraction from their hosts. Where there is iron in abundance such organisms would have a licence to multiply in an unbridled fashion at the expense of the host. Such a host, due to their increased iron load, would be able to harbour a high parasitic load which would be harmful to the population as a whole, not just the individual with the haemochromatosis allele. As man migrated from the tropics many of the larger pathogens disappeared and man had only to contend with traditional unicellular adversaries.Iron is a critical micronutrient that the host attempts to withhold for invading pathogens. We also advance the theory that the tropical anaemias including sickle cell trait, thalassaemia, glucose-6-phosphate dehydrogenase deficiency, and pyruvate kinase deficiency are an ingenious evolutionary means by the host of withholding iron from tropical pathogens while simultaneously avoiding the deleterious effects of frank iron deficiency and/or iron deficiency anaemia. The mechanism is essentially an immunological passive aggressive orchestrated by man kind.The distribution of the parasitic fauna dictates the distribution of the haemochromatosis genes - Corrected ProofOssie Ferdinand Uzoigwe10.1016/j.mehy.2008.12.057Medical Hypotheses (2010)2010-08-13Medical Hypotheses2010-08-13http://www.medical-hypotheses.com/article/PIIS0306987710002628/abstract?rss=yesSummary: Parkinson disease (PD) is a chronic progressive degenerative disorder that affects over 6million people worldwide. It is manifested by motor and psychiatric signs. The latter inflicts up to 88% of PD patients. With the prolongation of life expectancy, it is presumed that the prevalence of PD will further rise, together with comorbid depression. As a result, the need for an adequate therapeutic answer for compounded PD with depression is called for urgently.Several theories try to explain the trigger of depression in PD patients by impaired activity in dopamine, norepinephrine and serotonin systems.Various treatment to combat depressive symptoms in PD patients were proposed and are in use, with ambiguous results and disturbing side effects. These anti-depressive modalities include SSRI’s, SNRI, TCA, NRI and ECT.Dopamine agonists showed some anti-depressant activity in several studies in depressive PD, but may cause side effects such as dizziness, somnolence, confusion and even hallucinations. The role of dopamine agonists in the treatment of depression is still being explored because of no sufficient number of controlled studies in this area.Our hypothesis is to suggest NDRI – Bupropion – as the first line of treatment in PD patients with depression, in PD induced depression and/or in depression triggered by one of the treatments given for PD. Dual norepinephrine and dopamine reuptake inhibition is associated with unique clinical profile that compounds together anti-depressant efficacy without serotonin associated side effects such as weight gain, sedation, sexual dysfunction.Bupropion, as mainly dopaminergic and noradrenergic anti-depressant can alleviate therapeutically depressive symptoms associated with PD. Clinical controlled studies on Bupropion use in PD depressed patients are required to support this hypothesis.Bupropion as the treatment of choice in depression associated with Parkinson’s disease and it’s various treatments - Corrected ProofSergey Raskin, Rimona Durst10.1016/j.mehy.2010.07.024Medical Hypotheses (2010)2010-08-13Medical Hypotheses2010-08-13http://www.medical-hypotheses.com/article/PIIS0306987710002641/abstract?rss=yesSummary: Thoracolumbar burst fracture (TLBF) is a common type of spinal injuries and frequently causes spinal cord injury. The frequency of neurological deficits in all TLBF can reach up to 50–60%. The typical TLBF images seen on axial computerized tomography are the bone fragment projected into the spinal canal, which always persuade surgeons that the narrowed canal must compress the neural content and therefore is responsible for neurological deficits, with the corollary that surgical decompression of spinal canal is an essential therapeutic strategy for functional recovery. We hypothesize that in TLBF, traumatic canal stenosis is a predictive factor for neurological dysfunction and the surgical decompression is vital to the recovery of neurological function. After a review of the available evidences, we conclude that spinal canal stenosis is poorly correlated with neurological dysfunction in TLBF, and surgical decompression is not vital to the neurological recovery. Therefore, traumatic canal stenosis should not be an isolated indication for surgical decompression in TLBF.Traumatic canal stenosis should not be an indication for surgical decompression in thoracolumbar burst fracture - Corrected ProofXing Zhao, Xiang-Qian Fang, Feng-Dong Zhao, Shun-Wu Fan10.1016/j.mehy.2010.07.026Medical Hypotheses (2010)2010-08-13Medical Hypotheses2010-08-13http://www.medical-hypotheses.com/article/PIIS0306987710002653/abstract?rss=yesSummary: Mammary fistula (MF) is a disease characterised by recurrent draining abscesses around the areola. The aetiology of MF remains unclear. The most common cause is duct obstruction by squamous metaplasia. The clinical aspects and histological findings of MF are very similar to those observed in hidradenitis suppurativa (HS). We propose a new hypothesis on the pathogenesis of MF and suggest that occlusion of hair follicles by keratinous plugging may relevantly contribute to the development of MF.Follicular occlusion due to hyperkeratosis: A new hypothesis on the pathogenesis of mammillary fistula - Corrected ProofJuan D. Berná-Serna, Juan D. Berná-Mestre10.1016/j.mehy.2010.07.027Medical Hypotheses (2010)2010-08-13Medical Hypotheses2010-08-13http://www.medical-hypotheses.com/article/PIIS0306987710002720/abstract?rss=yesSummary: As sulfur containing thiols, alpha lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants and free radical scavengers capable of performing many of the same functions as glutathione (GSH). ALA supplementation may help protect mitochondria from oxidative stress, a possible mechanism contributing to certain forms of brain diseases called schizophrenia. Shortly before the advent of antipsychotic medications, two small studies found ALA relieved psychiatric symptoms in schizophrenia. More recently, animal studies have shown ALA augmentation improves mitochondrial function. At pharmaceutical levels, niacinamide helps preserve mitochondrial membrane integrity and acts as an antioxidant. ALA is a precursor for lipoamide, an essential mitochondrial coenzyme and niacinamide is a component of niacinamide adenine dinucleotide (NAD). NADH, the reduced form of NAD, is involved in the reduction of ALA to DHLA within the mitochondria. This is relevant to contemporary research because DHLA increases GSH and low GSH levels contribute to mitochondrial dysfunction and oxidative stress which have been implicated in the pathophysiology of schizophrenia.Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia? - Corrected ProofSheila E.J. Seybolt10.1016/j.mehy.2010.07.034Medical Hypotheses (2010)2010-08-13Medical Hypotheses2010-08-13http://www.medical-hypotheses.com/article/PIIS0306987710002689/abstract?rss=yesSummary: A high total plasma cholesterol concentration is the most common abnormality found in patients with kidney disease, which may be associated with the increased hepatic synthesis of apoB containing lipoproteins. ApoB mRNA editing plays an important physiological role in mammalian lipid metabolism by modifying the distribution of apoB-100 and apoB-48. However, it is regretful that apoB mRNA editing cannot be found in human liver because of the absence of apobec-1 expression. In this context, we hypothesize that the recapture of hepatic apoB mRNA editing may be a promising strategy to relieve nephrotic dyslipidemia. The data presented below focus on those which support this hypothesis with regards to evidence in vitro and in vivo. (1) Human wild-type apoB mRNA can be edited only when both apobec-1 and ACF proteins are presented simultaneously in vitro. (2) Adenoviral vectors can produce short-term expression of exogenous apobec-1 in the livers and lower plasma apoB-100 and LDL levels transiently. (3) Apobec-1 transgenic animals exhibit massive hepatic editing of apoB mRNA and fundamental decreased plasma levels of apoB-100 and LDL, but are exposed to high risk of liver dysplasia and hepatocellular carcinomas. In summary, taking into account the therapeutic security, we put forward that apobec-1 recombinant adenoviral vectors can be used for the recapture of hepatic apoB mRNA editing with a transient low-level manner and may achieve satisfactory lipid-lowing effect in nephropathic animals.Recapture of hepatic apolipoprotein B mRNA editing may be a promising strategy to relieve nephrotic dyslipidemia - Corrected ProofPeng Hu, Ling Lu, Bo Hu, Yuan Han Qin10.1016/j.mehy.2010.07.030Medical Hypotheses (2010)2010-08-12Medical Hypotheses2010-08-12http://www.medical-hypotheses.com/article/PIIS0306987710002343/abstract?rss=yesSummary: A sudden disappearance of cancer and all its signs and symptoms and markers without any medical intervention is considered as a spontaneous remission of cancer. In the past reports of spontaneous remission of cancer was dismissed as a misdiagnosis. Today, with so many bonafide reports of spontaneous remission of cancer (pathology, blood test, radio imaging, etc.) its existence is accepted by the medical community with any medical explanation.Spontaneous remission of cancer: Steady and aggressive malignant growth faced with hypoxia or hypoglycemia - Corrected ProofBehzad Niakan10.1016/j.mehy.2010.07.006Medical Hypotheses (2010)2010-08-11Medical Hypotheses2010-08-11http://www.medical-hypotheses.com/article/PIIS0306987710002616/abstract?rss=yesSummary: Decidual antigen-presenting cells including dendritic cells (DCs) and CD14+ macrophages, as mediators of the first encounter with fetal antigens, appear to be critically involved in the initiation of primary immune response by regulating innate- and adaptive immunity. Interleukin-15, produced by them, permits the proliferation and differentiation of CD3−CD16−CD94+NKG2A+CD56+bright decidual NK cells that identify trophoblast cells. These cells are able to kill them after Th1 cytokine overstimulation and by increasing the release of preformed cytotoxic mediators. Thus, the local microenvironment is a potent modulator of antigen-presenting cell functions. Tumor associated glycoprotein-72 (TAG-72) and mucine 1 (MUC-1) are glycoproteins secreted by uterine epithelial cells. Our hypothesis is that TAG-72 and MUC-1 are the natural ligands for carbohydrate recognition domains (CRDs) of endocytic mannose receptor (MR or CD206) and DC-specific ICAM non-integrin (DC-SIGN or CD209) expressed on decidual CD14+ macrophages and CD1a+ DCs. They might be able to condition antigen-presenting cells to produce distinct profiles of cyto/chemokines with consequential reduction in NK-cell numbers and cytotoxic potential leading to insufficient control over trophoblast growth. This hypothesis could explain the disappearance of MUC-1 beneath the attached embryo during the process of successful implantation when tight regulation of trophoblast invasion is needed. As IL-15 is the earliest and the most important factor in NK-cell proliferation, differentiation, and maturation, we expected primarily an increase of IL-15 expression in antigen-presenting cells concomitant with the disappearance of mucins and the enhancement in NK cells numbers and of cytotoxic potential after their close contact with early pregnancy decidual antigen-presenting cells. If our hypothesis is correct, it would contribute to the understanding of the role of mucins in the redirection of immune response via antigen-presenting cells and could help explain the mechanism of IL-15 regulation at the maternal–fetal interface of normal, ectopic-, and pathological pregnancies with effects on NK-cell proliferation, cytolytic mediator expression, and regulation of trophoblast growth control.Regulation of NK-cell function by mucins via antigen-presenting cells - Corrected ProofG. Laskarin, A. Redzovic, S. Srsen Medancic, D. Rukavina10.1016/j.mehy.2010.07.023Medical Hypotheses (2010)2010-08-11Medical Hypotheses2010-08-11http://www.medical-hypotheses.com/article/PIIS0306987710002677/abstract?rss=yesSummary: The study of pediatric catatonia has not received much attention. During the last few years, progress has been made in delineating this syndrome in children and adolescents across a wide range of disorders. Catatonia is a potentially life-threatening but treatable syndrome that also occurs in children and adolescents with autistic, developmental, and tic disorders, and in its idiopathic form. In many of these cases, catatonia cannot be accounted for by an associated psychotic, affective, or medical disorder. These findings are imminently relevant for classification where catatonia is currently restricted to sections of the psychotic, affective, or medical disorders. Catatonia should always be the primary diagnosis in children, adolescents, and adults, as specific treatments for catatonia, i.e., benzodiazepines and electroconvulsive therapy, lower risk of worsening catatonia or precipitating Neuroleptic Malignant Syndrome when antipsychotic medications are used as first-line or sole treatment. The creation of a separate diagnostic class for catatonia is the safest approach to ensure proper diagnosis and treatment of this syndrome in patients of all ages and the best approach to promote research.The study of pediatric catatonia supports a home of its own for catatonia in DSM-5 - Corrected ProofDirk Dhossche, David Cohen, Neera Ghaziuddin, Charmaine Wilson, Lee Elizabeth Wachtel10.1016/j.mehy.2010.07.029Medical Hypotheses (2010)2010-08-11Medical Hypotheses2010-08-11http://www.medical-hypotheses.com/article/PIIS0306987710002707/abstract?rss=yesThe consumption of arsenic was quite common in the 1800s. This metal was in fact prescribed for a myriad of diseases, and even as a beauty product or an aphrodisiac. Although its toxicity was well recognized, arsenic continued to be used for the preparation of drugs, and may be found even today within the homeopatic or the Chinese pharmacopeia.Arsenic eaters and altitude sickness: An epigenetic strategy for improving fitness in a hostile environment? - Corrected ProofLucio Tremolizzo, Michele A. Riva, Carlo Ferrarese10.1016/j.mehy.2010.07.032Medical Hypotheses (2010)2010-08-11Medical Hypotheses2010-08-11CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS0306987710002732/abstract?rss=yesSummary: Subacute sclerosing panencephalitis (SSPE) is a progressive devastating disease. Along with the slow measles virus infection, apoptotic cell death has shown to be one of the major mechanisms at the pathogenesis. Volume reduction in frontotemporal cortex has seen in patients at early stages of disease. At present, there is no effective treatment to completely cure SSPE. Oral isoprinosine and intrathecal or intraventricular alpha-interferon are anti viral therapies with limited success.Flupirtine is an anti apoptotic agent which has been used with limited success in Alzheimer disease, prion diseases and neuronal ceroid lipofuscinosis which is a inherited disease of apoptosis related genes. Therefore, we hypothesize that flupirtine with combination of antiviral therapy may halt the progressive course of the disease.Flupirtine may stop the progressive course of subacute sclerosing panencephalitis - Corrected ProofBurak Tatlı, Barış Ekici, Meral Özmen10.1016/j.mehy.2010.07.035Medical Hypotheses (2010)2010-08-11Medical Hypotheses2010-08-11http://www.medical-hypotheses.com/article/PIIS030698770900379X/abstract?rss=yesSummary: Migraine disorders are more prevalent among women than men. The ovarian neurosteroids play an important role in this sex difference by modulating neurotransmitter systems involving migraine pathogenesis. During perimenopause, unlike the postmenopausal period, women are under unstable fluctuations of ovarian neurosteroid levels. Such fluctuations might be an important interval-specific trigger for activating migraines. Along with migraine headache, dizziness is one of the most common complaints of perimenopause. A significant portion of this dizziness may be caused by vestibular migraine that has heterogeneous clinical features with dizziness and/or migraine headache. Because of this variation in phenomenology, the symptom of dizziness and vertigo during perimenopause is frequently misclassified as being a nonspecific climacteric symptom or having psychological origin. The recognition of vestibular migraine and its heterogeneous clinical presentations are important to understand, differentiate and correctly diagnose the symptom of dizziness and vertigo during perimenopausal transition. Further, recognition of the steroid influences on migraine genesis will lead to improved treatment regimens for vertigo from migraine.Vestibular migraine may be an important cause of dizziness/vertigo in perimenopausal period - Corrected ProofJ.H. Park, E. Viirre10.1016/j.mehy.2009.04.054Medical Hypotheses (2010)2010-08-09Medical Hypotheses2010-08-09http://www.medical-hypotheses.com/article/PIIS0306987710002318/abstract?rss=yesSummary: Fibromyalgia is a condition characterized by long term body-wide pain and tender points in joints, muscles and soft tissues. Other symptoms include chronic fatigue, morning stiffness, and depression. It is well known that these symptoms are exacerbated under periods of high stress. When pain becomes severe enough, the mind can enter what is known as a dissociative state, characterized by depersonalization – the feeling of detachment from one’s physical body and the illusion of watching one’s physical body from outside. In evolutionary terms, dissociative states are thought to be an adaptive mechanism to mentally distance oneself from pain, often during trauma. Similar dissociative experiences are reported by subjects who have used psychoactive drugs such as ketamine. We have previously used non-invasive mirror visual feedback to treat subjects with chronic pain from phantom limbs and suggested its use for complex regional pain syndrome: once considered intractable pain. We wondered whether such methods would work to alleviate the chronic pain of fibromyalgia. We tested mirror visual feedback on one fibromyalgia patient. On 15 trials, the patient’s lower limb pain rating (on a scale from 1 to 10) decreased significantly. These preliminary results suggest that non-invasive dissociative anesthetics such as VR goggles, ketamine, and mirror visual feedback could be used to alleviate chronic pain from fibromyalgia. This would furnish us with a better understanding of the mechanism by which external visual feedback interacts with the internal physical manifestation of pain.Using mirror visual feedback and virtual reality to treat fibromyalgia - Corrected ProofV.S. Ramachandran, Elizabeth L. Seckel10.1016/j.mehy.2010.07.003Medical Hypotheses (2010)2010-08-09Medical Hypotheses2010-08-09http://www.medical-hypotheses.com/article/PIIS0306987710002355/abstract?rss=yesSummary: Stem cells, which reside in most tissues with high plasticity of self-renewal and differentiation, play a critical role in the development and maintenance processes of many tissues. It is reasonable to suspect that many undefined chronic diseases are caused by the malfunction of stem cells. In this hypothesis, we try to explain the origin of undefined chronic diseases by the developmental plasticity of stem cells. Chronic diseases are phenotypes of stem cells’ malfunction. Mutations of multipotent stem cells at the prenatal stage can be used to explain phenomena of early development of diseases. In addition, stem cells accumulate mutations from fetus stage to aging period and usually develop chronic diseases in late life periods.Developmental plasticity of stem cells and diseases - Corrected ProofGuopei Luo, Jiang Long, Bo Zhang, Chen Liu, Jin Xu, Xianjun Yu, Quanxing Ni10.1016/j.mehy.2010.07.007Medical Hypotheses (2010)2010-08-06Medical Hypotheses2010-08-06http://www.medical-hypotheses.com/article/PIIS0306987710002598/abstract?rss=yesA number of cases have been reported of antibiotic-induced psychosis . A search of the internet and Pub Med without an attempt to be comprehensive revealed over 25 published reports spanning the period of 1995–2009. In a review of over a 100 published and WHO and FDA-reported cases of antibiotic-induced mania (termed ‘antibiomania’ by the reviewers), it is noted that many of these individuals exhibited psychotic symptoms as well . In the majority of cases, the symptoms resolved after termination of the antibiotic treatment, and returned upon its reintroduction, suggesting a causal relationship.Antibiotic-induced psychosis: A link to d-alanine? - Corrected ProofShujaath Mehdi10.1016/j.mehy.2010.07.021Medical Hypotheses (2010)2010-08-06Medical Hypotheses2010-08-06CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS0306987710002306/abstract?rss=yesSummary: Oral lichen planus (OLP) is a chronic inflammatory disease, which has been defined by the World Health Organization as a potential precancerous condition, representing a generalized state associated with a significantly increased risk of oral cancer. We would like to put forward a hypothesis that inflammatory mediators such as cytokines and chemokines released from infiltrating T lymphocytes induce fundamental changes of proteins in oral epithelial cells, leading to the progression of OLP to oral squamous cell carcinoma (OSCC). These altered proteins can act as the key risk factors associated with the local microenvironment and development of OSCC. Identification of these proteins would add to our understanding of the connection between chronic inflammation and OSCC.Oral lichen planus is a unique disease model for studying chronic inflammation and oral cancer - Corrected ProofYi Liu, Diana V. Messadi, Hongkun Wu, Shen Hu10.1016/j.mehy.2010.07.002Medical Hypotheses (2010)2010-08-02Medical Hypotheses2010-08-02http://www.medical-hypotheses.com/article/PIIS0306987710002367/abstract?rss=yesTopical photodynamic therapy (PDT) is currently used in dermatology in the management of premalignant and malignant skin lesions with a high efficacy . PDT is based on the local application of 5-aminolevulinic acid (ALA) or methyl-aminolevulinic acid (MAL) on tumoral or inflamed skin lesions. ALA and MAL are porphyrin precursors that are converted by the haem biosynthetic pathway to protoporphyrin IX (PpIX) in atypical cells. When exposed to light of the appropriate wavelengths, PpIX undergoes photochemical degradation and releases cytotoxic oxygen radicals that result in selective cell necrosis and/or apoptosis . Clinical research is nowadays focusing on widening its range of indications to various non-oncological cutaneous indications. Among these, PDT has been proposed in cutaneous leishmaniasis (CL) with seeming good success as the British Association of Dermatology guidelines considered there was fair evidence to support the use of this procedure in CL . CL is a chronic cutaneous infection caused by parasites belonging to the genus Leishmania transmitted by the bite of sandflies. Despite spontaneous resolution of the skin lesions, CL may lead to disfiguring scars . Numerous local and systemic treatments have been proposed without any universal approach in order to reduce lesion size, promote healing with minimal scarring and also eradicate the amastigotes.Efficacy of photodynamic therapy in cutaneous leishmaniasis: A “hidden” local heat effect? - Corrected ProofNicolas Kluger, Céline Girard, Anca Debu, Bernard Guillot10.1016/j.mehy.2010.07.008Medical Hypotheses (2010)2010-08-02Medical Hypotheses2010-08-02CORRESPONDENCEhttp://www.medical-hypotheses.com/article/PIIS0306987710002379/abstract?rss=yesSummary: Our hypothesis concerns the chronic activation of macrophages, and the continual production of pro-fibrotic tissue repair factors, as a cause of digital clubbing in an array of pulmonary pathologies. The level of macrophage activation will differ between individuals, corresponding to the variable immune response to these pulmonary pathologies. Due to this variability, there is a corresponding inconsistency in the presentation of clubbing. Although testing of this hypothesis would be difficult, there is evidence to support our theory; including a link to chronic diseases involving granulomas, where there would be a large collection of macrophages present and pathologies in organs with large resident macrophage populations. This theory, therefore, could also be developed to include non-pulmonary causes of clubbing.A new hypothesis on the mechanism of digital clubbing secondary to pulmonary pathologies - Corrected ProofOliver T.R. Toovey, Helen J. Eisenhauer10.1016/j.mehy.2010.07.009Medical Hypotheses (2010)2010-08-02Medical Hypotheses2010-08-02