Medical Hypotheses (MED HYPOTHESES )

Publisher: Elsevier

Description

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

  • Impact factor
    1.18
    Show impact factor history
     
    Impact factor
  • 5-year impact
    1.16
  • Cited half-life
    5.90
  • Immediacy index
    0.25
  • Eigenfactor
    0.01
  • Article influence
    0.32
  • Website
    Medical Hypotheses website
  • Other titles
    Medical hypotheses
  • ISSN
    0306-9877
  • OCLC
    1357097
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Elsevier

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

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Remote ischaemic preconditioning is emerging as a promising clinical technique which can afford immediate protection against coronary ischaemia. The mechanisms which mediate the signal transduction from remote organ to the heart are still unclear. The role of ATP sensitive potassium channels in ischaemic preconditioning has been established. It is known that the red blood cell (RBC) acts as a mediator of local autoregulation in adjusting oxygen supply to demand by sensing hypoxia and releasing ATP locally to achieve vasodilatation in the adjacent vascular beds. Our hypothesis links these two known mechanisms. Remote ischaemic preconditioning and local RBC autoregulation might share a common mechanism using the ATP sensitive potassium channels. Therefore, we hypothesize that the signal transduction by RBC might be partly responsible for this protection against ischaemia.
    Medical Hypotheses 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The inorganic sulfur content of the Western Diet is more than six times greater than the minimal daily requirement. The non-adsorbed organic and inorganic sulfur supports high levels of sulfate reducing bacteria (SRB) in the large intestine. Over time, the combination of elevated dietary inorganic sulfur and high levels of SRB in the gut increases the potential of ultra-exogenous sulfide formation (USF). High levels of SRB in the right colon can sustain USF that overwhelms sulfide oxidation by the colon and sulfide enters into the capillary network of the right colon. White blood cells and platelets in this capillary network are exposed to the elevated sulfide concentration, which induces these cells to generate reactive oxygen species (ROS). An estimated 1.3% of the total cardiac output is impacted by the elevated sulfide every minute. USF for 10 and 78 minutes per day could generate the 12% and 64% of ROS-positive blood cells that were observed in the arterial blood samples of non-hospitalized volunteers and congestive heart failure patients, respectively. More extreme USF is necessary to generate greater percentages of ROS-positive blood cells, since the recirculated blood will provide sulfide oxidation. The dietary inorganic sulfur consumption pattern dictates the abundance of SRB in the gut and therefore, the percent of ROS-positive blood cells. Exposure of blood to a range of sulfide levels may determine the minimum sulfide concentration necessary to generate ROS-positive blood cells. After validation, patients with high levels of ROS-positive blood cells can be evaluated for reduction of oxidative stress by dietary inorganic sulfur control. If USF is confirmed as the source of ROS-positive blood cells, then the problem of oxidative stress becomes manageable through dietary changes, metals supplements, methanogenic probiotics, and antibiotics that target SRB.
    Medical Hypotheses 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by generalized microvascular occlusion. TTP has been related to severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor multimers into less adhesive molecules. However, ADAMTS13 deficiency correlates poorly with severity of thrombocytopenia or microangiopathic hemolysis, with the frequency of neurologic complications or the response to plasma exchange. Also, some patients with severe hereditary ADAMTS13 deficiency consistently relapse every few weeks, whereas others remain asymptomatic into their forties. Taken together, these findings suggest that an additional element is missing in the pathophysiology of TTP. We postulate that both low ADAMTS13 activity and low tissue-plasminogen activator activity are required to trigger TTP attacks. Tissue-plasminogen activator end product, plasmin, extensively degrades von Willebrand factor, breaking-down the bonds between platelets and the blood vessel wall, so that low tissue-plasminogen activator activity prevents a mechanism similar to that of ADAMTS13. The hypothesis that low tissue-plasminogen activator activity plays an important role in TTP pathogenesis is further substantiated by TTP comorbidity. Problems prevalent in patients with TTP attacks or with long-term TTP remission, including increased body mass index, major depression, cognitive abnormalities, hypertension, and premature death, are somehow associated with low tissue-plasminogen activator activity.
    Medical Hypotheses 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of currently available guidelines such as the International Classification of Diseases, 10th Revision (ICD-10) and its clinical modification to assign a principal diagnosis to a patient who has multiple principal diagnoses appears unreliable. This is because these guidelines are complex and uses criteria that are highly subjective. Even when one main diagnosis is selected, the comprehensive list of other diseases that the patient has is often not reported such that the overall clinical condition of the patient is obscured. To address these issues, we have proposed: (i) a simple, potentially reliable and stepwise guide that can be used to assign the single most appropriate main principal diagnosis to each patient and illustrated this with case reports (ii) how to simultaneously report the main and other diagnoses in a scientific paper. It is hoped that our proposal (named NJ model for easy referencing) will help standardize how diagnosis is assigned to patients. � 2014 Elsevier Ltd. All rights reserved.
    Medical Hypotheses 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An understanding of heart-circulation interaction is crucial to our ability to guide our patients through an episode of septic shock. Our knowledge has advanced greatly in the last one hundred years. There are, however, certain empirical phenomena that may lead us to question the wisdom of our prevailing treatment algorithm. Three extreme but iatrogenically possible haemodynamic states exist. Firstly, inappropriately low venous return; secondly, overzealous arteriolar constriction; and finally, misguided inotropy and chronotropy. Following an unsuccessful fluid challenge, it would be logical to first set the venous tone, then set the cardiac rate and contractility, and finally set the peripheral vascular resistance. It is hypothesized that a combination of dihydroergotamine, milrinone and esmolol should be superior to a combination of noradrenaline and dobutamine for surviving sepsis.
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Migraine is a chronic recurring headache for which no complete treatment has been found yet. Therefore, finding new treatment approaches and medicines is important. In this review, we consider the probable mechanism of action of a traditional and ethnic formulary of chamomile extract in sesame oil as a new topical medication for migraine pain relief. Chamomile oil is prepared in traditional Persian medicine by boiling aqueous extract of chamomile in sesame oil. To optimize the procedure, we can use a Clevenger-type apparatus to extract the essential oil and add it to the end product. The preparation includes both essential oils (chamazulene and bisabolol oxide) and polyphenols (a flavonoid such as apigenin and its derivatives). It probably possesses pain relief effects for migraines because of the following properties: 1) chamazulene and apigenin, which inhibit iNOS expression in activated macrophages and can lead to the prohibition of NO release and synthesis; 2) chamomile flavonoids, which have a strong inhibitory effect on endogenous prostaglandin E2 (PGE2) levels in RAW 264.7 macrophages and can play the role of selective COX-2 inhibitor; 3) chamomile polyphenols, which possess anti-inflammatory effects due to the inhibition of pro-inflammatory biomarkers in THP1 macrophages and which can reduce inflammation in neurovascular units (NVU) at the site of migraine pain; 4) chamomile, which has neuroprotective effects because of reduced NO levels; 5) sesamine in sesame oil, which possesses an anti-inflammatory effect. These effects are supported by main pathophysiology theories of migraine such as neural and sensitization theories. Chamomile oil is a traditional formulation still used in Iran as an ethno-medicine. Because of the mentioned mechanisms of action, it can be hypothesized that chamomile oil is a novel medicine for the relief of migraine pain.
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pressure ulcers are one of the most common causes of morbidity, mortality and rehospitalization for those living with Spinal Cord Injury (SCI). Literature examining risk and recurrence of pressure ulcers (PrUs) has primarily focused on the nursing home elderly who do not have SCI. More than 200 factors that increase PrU risk have been identified. Yet unlike the elderly who incur pressure ulcers in nursing homes or when hospitalized, most persons with SCI develop their pressure ulcers as outpatients, while residing in the community. The Veterans Health Administration (VHA) provides medical care for a large number of persons with chronic SCI. Included in the VHA SCI model of chronic disease management is the provision of an annual Comprehensive Preventive Health Evaluation, a tool that has potential to identify individuals at high risk for PrUs. This research was motivated by the clinical observation that some individuals appear to be protected from developing PrUs despite apparently ‘risky’ behaviors while others develop PrUs despite vigilant use of the currently known preventative measures. There is limited literature regarding protective factors and specific risk factors that reduce PrU occurrence in the community dwelling person with chronic SCI have not been delineated. The purpose of this study is to examine the preliminary hypothesis that there are biological and/or psychosocial factors that increase or reduce vulnerability to PrUs among persons with SCI. A limited number of refined hypotheses will be generated for testing in a prospective fashion. A retrospective cross-sectional survey of 119 randomly selected Veterans with SCI undergoing the Comprehensive Health Prevention Evaluation during the year 2009 was performed. Factors that differed between patients with 0, 1 or ⩾ 2 PrUs were identified and stratified, with an emphasis on modifiable risk factors. Three hypotheses generated from this study warrant further investigation: 1) Cumulative smoking history increases the risk of PrUs independent of co-morbidities, 2) Being moderately overweight, BMI>25, with or without spasticity, is a modifiable factor that may be protective and 3) Increased use of a caregiver does not reduce PrU risk. Prospective studies that focus on these hypotheses will lead to evidence-based risk assessment tools and customized interventions to prevent PrUs in persons with SCI in the outpatient setting.
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human stem cells possess memory, and consequently all living human cells must have a memory system. How memory is stored in cells and organisms is an open question. Magnetite is perhaps the best candidate to be a universal memory molecule. Magnetite may give us a clue, because it is the Earth’s most distributed and important magnetic material. It is found in living organisms with no known functions except for involvement in navigation in some organisms. In humans magnetite is found in the brain, heart, liver and spleen. Humans suffer from memory dysfunctions in many cases when iron is out of balance. Anomalous concentrations of magnetite is known to be associated with a neurodegenerative disorder like Alzheimer’s disease. Due to the rapid speed and accuracy of our brain, memory and its functions must be governed by quantum mechanics.
    Medical Hypotheses 09/2014;
  • Source
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Endotoxic lipopolysaccharide (LPS) is a major constituent of the outer membrane of the gram-negative bacillus, and its’ release a potent pro-inflammatory stimulus. Unchecked the cytokine cascades unleashed by blood borne LPS leads to clinical manifestations of severe sepsis and septic shock. Experimentally exogenous administration of cell-wall specific bacteriocidal drugs are known to precipitate endotoxin release and contribute to development of the sepsis syndrome. Mitigation of the inflammatory septic response with intravenous infusion of phospholipid emulsion has been demonstrated in vivo, with phospholipid credited with binding and neutralizing circulating endotoxin. We therefore propose co-administration of phospholipid emulsion preparations in conjunction with potent cell wall specific antibacterial agents in gram-negative sepsis – hypothesizing that released LPS may be immediately sequestered by phospholipid thereby blunting the severity of the developing septic response.
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer’s disease (AD) is the most common form of dementia characterized by deterioration of memory and other cognitive domains which leads to death in 3-9 years after diagnosis. In addition to mutations in APP, PSEN1 and PSEN2 genes, that cause early onset autosomal dominant AD, several genetic risk factors for late onset AD are now known. There is another distinctive neurodegenerative lysosomal storage disorder- Niemann-Pick type C (NPC) that is sometimes referred to as “Childhood Alzheimer’s”. NPC is autosomal recessive disease caused by mutations in the NPC1 or NPC2 genes. NPC and AD share some biochemical and pathological similarities which are discussed in this paper. On the other hand, there is a well documented connection between other autosomal recessive lysosomal storage disorder – Gaucher’s disease (GD) and neurodegenerative disorder- Parkinson’s disease (PD). It has been shown that GD patients have 20 fold increased life-time risk of developing PD. Surprisingly, even heterozygous carriers of mutations in glucocerebrosidase gene (GBA) have increased risk for developing PD. Having in mind above mentioned correlations, we hypothesized that heterozygous mutations in the NPC gene may act as an independent risk factor for Alzhemer’s disease. If true, this would expand link between lysosomal disorders and neurodegenerative diseases. Also, if heterozygous NPC1/2 mutation carriers develop AD we assume it would be worth trying with miglustat- specific therapy recommended for NPC disease.
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Perfusion experiments on an isolated, canine lateral saphenous vein segment preparation have shown that noradrenaline causes potent, flow dependent effects, at a threshold concentration comparable to that of plasma noradrenaline, when it stimulates the segment by diffusion from its microcirculation (vasa vasorum). The effects caused are opposite to those neuronal noradrenaline causes in vivo and that, in the light of the principle that all information is transmitted in patterns that need contrast to be detected – star patterns need darkness, sound patterns, quietness – has generated the hypothesis that plasma noradrenaline provides the obligatory contrast tissues need to detect and respond to the regulatory information encrypted in the diffusion pattern of neuronal noradrenaline. Based on the implications of that hypothesis, the controlled variable of the peripheral noradrenergic system is believed to be the maintenance of a set point balance between the contrasting effects of plasma and neuronal noradrenaline on a tissue. The hypothalamic sympathetic centres are believed to monitor that balance through the level of afferent sympathetic traffic they receive from a tissue and to correct any deviation it detects in the balance by adjusting the level of efferent sympathetic input it projects to the tissue. The failure of the centres to maintain the correct balance, for reasons intrinsic or extrinsic to themselves, is believed to be responsible for degenerative and genetic disorders. When the failure causes the balance to be polarised in favour of the effect of plasma noradrenaline that is believed to cause inflammatory diseases like dilator cardiac failure, renal hypertension, varicose veins and aneurysms; when it causes it to be polarised in favour of the effect of neuronal noradrenaline that is believed to cause genetic diseases like hypertrophic cardiopathy, pulmonary hypertension and stenoses and when, in pregnancy, a factor causes the polarity to favour plasma noradrenaline in all the maternal tissues except the uterus and conceptus, where it favours neuronal noradrenaline, that is believed to cause preeclampsia.
    Medical Hypotheses 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegenerative diseases are a group of central nervous system diseases that have a high rate of morbidity and mortality. More disabling than lethal, the pathogenesis of many of these diseas-es, like Alzheimers disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyo-trophic lateral sclerosis (ALS) and Multiple sclerosis, (MS) remains to be established. Even after passage of several decades subsequent to their first recognition, these diseases have proven to be notoriously refractory towards drug treatment. Stem cell therapy itself has faced problems like ethical issues with such transplants, difficult and risky implantation routes and immune rejections of the implanted stem cells. Somatic Cell Nuclear Transfer (SCNT) offers a hope to the aforesaid diseases if the cells selected for nuclear donation itself has inherent regenerative and scavenging properties. Here we propose olfactory ensheathing cells (OEC’s) as the donor somatic cell that conceivably would attempt regeneration in above mentioned diseases by differentiating into glia, which would have healthy mitochondria and without any fear of immune rejection. Also proposed is a method of delivering these cells after SCNT to the brain by a novel “transcribrial route” through a device that can deliver cells to the brain across the cribriform plate of ethmoid bone.
    Medical Hypotheses 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Despite aggressive treatment with anti-rheumatic drugs, progressive destruction of joints continues to occur in RA patients, who subsequently require joint surgery. A lot of evidence suggest that fibroblast-like synovial cells (FLS) play crucial role in joint degradation and the propagation of inflammation in RA. The expansion of fibroblast populations in the joint results primarily from the inhibition of pro-apoptotic pathways, rather than large scale proliferation. Because multiple factors, which contribute to fibroblast activation and enhance their destructive potential, are under control of transcription factor NF-κB, this pathway presents an interesting target for RA therapy. However, due to the lack of specificity, NF-κB inhibitors may exert severe side effects. Given the above, there has recently been more interest in natural substances of plant origin which are regarded as a safe alternatives for synthetic drugs. Mangiferin, the naturally occurring polyphenol with excellent anti-inflammatory and antioxidative properties, exhibits strong pro-apoptotic effect toward synoviocytes isolated from human synovia. Moreover, it shows no cytotoxicity toward cultivated chondrocytes and reduces the levels of matrix metalloproteinases. Considering that mangiferin is a natural constituent of foods and traditional herbal medicines, showing fewer adverse effects and low toxicity, we hypothesize that it may prove effective in the treatment of RA and prevention against joint destruction.
    Medical Hypotheses 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Compelling new findings suggest that an early core signature of autism is a deficient left anterior temporal lobe response to language and an atypical over-activation of the right anterior temporal lobe. Intriguingly, our recent results from an entirely different line of reasoning and experiments also show that applying cathodal stimulation (suppressing) at the left anterior temporal lobe together with anodal stimulation (facilitating) at the right anterior temporal lobe, by transcranial direct current stimulation (tDCS), can induce some autistic-like cognitive abilities in otherwise normal adults. If we could briefly induce autistic like cognitive abilities in healthy individuals, it follows that we might be able to mitigate some autistic traits by reversing the above stimulation protocol, in an attempt to restore the typical dominance of the left anterior temporal lobe. Accordingly, we hypothesize that at least some autistic traits can be mitigated, by applying anodal stimulation (facilitating) at the left anterior temporal lobe together with cathodal stimulation (suppressing) at the right anterior temporal lobe. Our hypothesis is supported by strong convergent evidence that autistic symptoms can emerge and later reverse due to the onset and subsequent recovery of various temporal lobe (predominantly the left) pathologies. It is also consistent with evidence that the temporal lobes (especially the left) are a conceptual hub, critical for extracting meaning from lower level sensory information to form a coherent representation, and that a deficit in the temporal lobes underlies autistic traits.
    Medical Hypotheses 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tumor-initiating cells(TICs) are a subpopulation of chemoresistant tumor cells that have been shown to cause tumor recurrence. Targeting and eliminating of TICs are therefore priorities for the development of new therapeutic paradigms. Much promise lies in adoptive immunotherapy. Cytokine-induced killer (CIK) cells are heterogeneous ex vivo-expanded T lymphocytes, with a mixed T-NK phenotype. It represents a realistic new option in the field of Hepatocellular carcinoma(HCC) immunotherapy. In the very recent years, Large clinical trials demonstrated that CIK cells could improve the Progression Free Survival (PFS) and Overall Survival(OS) in patients with HCC. By the same time, several studies reported that CIK cells were capable of clearing cells with stemness features in Lymphoma, Melanoma, Bone and Soft-Tissue Sarcomas. Based on the findings above mentioned, we hypothesized that CIK cells could eliminate the tumor-initiating cells, improving the PFS and OS of patients with HCC when combined with radiofrequency ablation(RFA) or transcatheter arterial chemoembolization(TACE).
    Medical Hypotheses 08/2014;